Corneal structure and transparency

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

The corneal epithelium is about 53 μm deep and constitutes about 10% of the corneal thickness.

“The corneal epithelium, on the other hand, is about 53 μm deep (Reinstein et al., 2008) and thus constitutes about 10% of the corneal thickness.”

• cites Reinstein et al., 2008 sourceSupported

May combine two claims.

Second harmonic generation imaging can provide qualitative and quantitative information about lamellar organisation within the cornea and has the potential to be used in vivo.

“Over the last decade there has been an upsurge in the use of non-linear microscopy, in particular second harmonic generation imaging, to provide qualitative (Han et al., 2005, Morishige et al., 2006, Teng et al., 2006, Bueno et al., 2011) and quantitative (Mega et al., 2012, Tuer et al., 2012, Ghazaryan et al., 2013) information about the lamellar organisation within the cornea, a technique that,”

• cites Han et al., 2005 sourceSupported
• cites Mega et al., 2012 sourcePartly supported

  The paper’s Abstract describes a method for quantifying collagen-lamellar orientation in corneal SHG images, supporting the quantitative part for which Mega et al. is cited. The experiments used a bovine cornea placed on a microscope cover slip; our copy does not establish the claimed potential for in vivo use. In the printed sentence, the qualitative citations are to other papers. (LLM, conf=0.86)

  Experimental — accuracy not yet measured
• cites Latour et al., 2012 sourceSupported

May combine two claims.

The posterior stroma can swell easily whereas the more interwoven anterior stroma cannot.

“The posterior stroma can swell easily whereas the more interwoven anterior cannot (Müller et al., 2001).”

• cites Müller et al., 2001 sourceSupported

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

At the nanoscopic level, corneal transparency is defined by the absence of pigments or blood vessels (in most species), and by the structure and organisation of the collagen fibrils within the lamellae.

“and at the nanoscopic level, by the absence of pigments or blood vessels (in most species), and by the structure and organisation of the collagen fibrils within the lamellae (Meek et al., 2003).”

• cites Meek et al., 2003 sourcePartly supported

  The discussion of corneal transparency (pp. 2–3) links light transmission to the structure and arrangement of collagen fibrils within lamellae. Our copy does not state that transparency depends on the absence of pigments or blood vessels, including the qualification about most species. (LLM, conf=0.88)

  Experimental — accuracy not yet measured

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Mammalian corneas do not have an orthogonal arrangement of adjacent lamellae, whereas non-mammalian vertebrate corneas share a common orthogonal collagen structural organisation, suggesting a divergent evolutionary background.

“The technique was recently used to show that mammalian corneas do not have an orthogonal arrangement of adjacent lamellae, whereas non-mammalian vertebrate corneas share a common orthogonal collagen structural organisation, which suggests that they have a divergent evolutionary background (Winkler et al., 2015).”

• cites Winkler et al., 2015 sourceSupported

May combine two claims.

Across the anterior stroma, lamellae are highly interwoven and randomly directed when observed en face.

“Across the anterior stroma, lamellae are highly interwoven (Radner et al., 1998) and randomly directed when observed en face (Abahussin et al., 2009).”

• cites Radner et al., 1998 sourceNot checked — no full text of the source
• cites Abahussin et al., 2009 sourceSupported

Probably not a substantial claim: may not pass S3 (load-bearing).

Corneal transparency is defined at the microscopic level by the absence of scatter by corneal cells or by other structures that could cause local changes to the refractive index.

“this property is defined at the microscopic level by the absence of scatter by corneal cells or by other structures that could cause local changes to the refractive index”

• cites Meek et al., 2003 sourcePartly supported

  The Direct summation of fields method section (p. 5) links low scattering by corneal cells to their refractive indices, but calls the cells weak scatterers—not non-scatterers—and notes that their nuclei scatter. The discussion on p. 3 also says collagen fibrils scatter light because their refractive index differs from the surrounding material; transparency involves interference of that scattered light. Thus the paper supports the importance of limiting scatter, but not the claimed microscopic absence of it. (LLM, conf=0.84)

  Experimental — accuracy not yet measured

May combine two claims.

The cross-linked rope-like structure with alternating twist at each hierarchical level conveys considerable strength to the narrow corneal fibrils, in contrast to the fibrils in the adjacent sclera, which are wider and have a more parallel arrangement of microfibrils.

“This cross-linked rope-like structure with alternating twist at each hierarchical level conveys considerable strength to the narrow corneal fibrils, and is in contrast to the fibrils in the adjacent sclera, which are correspondingly wider and therefore have a more parallel arrangement of microfibrils within them (Yamamoto et al., 2000).”

• cites Yamamoto et al., 2000 sourcePartly supported

  Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  Experimental — accuracy not yet measured

May combine two claims.

Three-dimensional electron tomographic reconstructions of bovine cornea showed that collagen fibrils were not lying on a perfect hexagonal lattice and that there was nothing systematic in the geometry of connections of adjacent or next nearest collagen fibrils.

“From the reconstructions, it was evident that the collagen fibrils were not laying on a perfect hexagonal lattice, and also that there was nothing systematic in the geometry of the connections of adjacent or next nearest collagen fibrils.”

• cites Lewis et al., 2010 sourceSupported

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Fibromodulin plays a major role in development of the peripheral cornea but its presence in the normal cornea is uncertain.

“fibromodulin plays a major role in development of the peripheral cornea but its presence in the normal cornea is uncertain (Chen et al., 2010).”

• cites Chen et al., 2010 sourcePartly supported

  The Discussion supports an important role for fibromodulin in peripheral corneal development. But although the Results call its presence in mature corneal stroma controversial, the paper then reports barely detectable levels at P90 and concludes that fibromodulin is not a component of mature corneal stroma. It does not leave its presence in the adult cornea uncertain. (LLM, conf=0.88)

  Experimental — accuracy not yet measured

May combine two claims.

Microfibrils have a right-handed twist within the fibrils and are stabilised by covalent intermolecular and intramolecular crosslinks.

“Microfibrils have a right-handed twist within the fibrils (Orgel et al., 2006), and are stabilised by covalent intermolecular and intramolecular crosslinks (Yamauchi et al., 1996).”

• cites Orgel et al., 2006 sourceSupported
• cites Yamauchi et al., 1996 sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Doutch (2009) found that a Fibonacci quasi-crystalline fibril arrangement closely resembles collagen fibril organization seen in micrographs and that the wavelength dependence of its predicted transparency matches the experimental one very closely.

“Doutch found that not only does its appearance closely resemble the collagen fibril organization seen in micrographs, but also that the wavelength dependence of the predicted transparency matches very closely the experimental one.”

• cites Doutch (2009)Supported

May combine two claims.

The surface gaps are a primary binding site for dermatan sulphate-containing proteoglycans, which are necessary for preventing adjacent fibrils from fusing together.

“They are also a primary binding site for dermatan sulphate-containing proteoglycans (Scott and Haigh, 1988), which, as we will also see later, are necessary for preventing adjacent fibrils from fusing together (Chen and Birk, 2013).”

• cites Scott and Haigh, 1988 sourceSupported
• cites Chen and Birk, 2013 sourcePartly supported

  The section “Instructive roles in collagen fibrillogenesis” (page unavailable) says that proteoglycan glycosaminoglycans extend into the space between fibrils and can influence their spacing and organization. It does not say that dermatan sulphate-containing proteoglycans are necessary to prevent adjacent fibrils from fusing. The surface-binding-site clause is cited to Scott and Haigh, not Chen and Birk, and is not judged here. (LLM, conf=0.84)

  Experimental — accuracy not yet measured

May combine two claims.

Keratocytes are regarded as quiescent but can be activated after injury, generating myofibroblast precursors that can persist and cause corneal scarring due to their own opacity and production of fibrotic tissue.

“The keratocytes are regarded as being quiescent but can be activated after injury generating myofibroblast precursors that can sometimes persist and cause corneal scarring due to their own opacity as well as their production of fibrotic tissue (Torreicelli and Wilson, 2014).”

• cites Torreicelli and Wilson, 2014 sourceSupported

May combine two claims.

Corneal structural defects of this type are associated with genetic mutations involving proteoglycans, which seem to affect the repulsive forces between adjacent fibrils and allow them to fuse.

“Corneal structural defects of this type are associated, for example, with genetic mutations involving proteoglycans (Chakravarti et al., 1998) which, ultimately, seem to have an effect on the repulsive forces between adjacent fibrils and allow them to fuse together.”

• cites Chakravarti et al., 1998 sourcePartly supported

  The Discussion reports corneal opacity in mice with a null mutation of the lumican gene, and its collagen-fibril section describes frequent lateral fusion of fibrils. The paper proposes that proteoglycan core proteins discourage lateral fusion, but it does not identify a change in repulsive forces between adjacent fibrils as the mechanism. (LLM, conf=0.85)

  Experimental — accuracy not yet measured

May combine two claims.

UV transmission through the cornea decreases from the centre to the periphery, attributed to a combination of scattering and absorption.

“We found that UV transmission through the cornea decreases from the centre to the periphery, and attributed this to a combination of scattering and absorption (Doutch et al., 2012).”

• cites Doutch et al., 2012 sourceSupported

May combine two claims.

The Cheng and Pinsky mechanism operates regardless of the direction of the perturbation and regardless of whether GAG chains are part of a duplex or are independent.

“Their mechanism, illustrated in Fig. 11, operates regardless of the direction of the perturbation and regardless of whether GAG chains are part of a duplex or are independent.”

• cites Cheng and Pinsky (2013) sourceSupported

May combine two claims.

Cheng and Pinsky (2013) concluded that ions attracted by the unbalanced charge on the glycosaminoglycan chains of interfibrillar proteoglycans play a dominant role in keeping fibrils on optimal lattice positions by acting as restoring forces, and that these forces by themselves can reproduce the image distribution of fibrils seen in the electron microscope.

“On the other hand, the ions attracted by the unbalanced charge on the glycosaminoglycan chains of the interfibrillar PGs play a dominant role in keeping the fibrils on optimal lattice positions, by acting as restoring forces, and the authors showed that these, by themselves, can reproduce the image distribution of fibrils seen in the electron microscope.”

• cites Cheng and Pinsky (2013) sourceSupported

May combine two claims.

In vitro, fibrils formed by collagen I and collagen V are larger than those found in vivo, indicating additional mechanisms such as microfibrillar coiling or collagen-bound disaccharides regulate fibril diameter.

“However, it was noticed that, in vitro, the fibrils formed by collagen I and collagen V are larger than those found in vivo. This indicates that there may be additional mechanisms such as microfibrillar coiling (Raspanti, 2010) or collagen-bound disaccharides (Harding et al., 1980) that regulate fibril diameter.”

• cites Raspanti, 2010 sourceSupported
• cites Harding et al., 1980Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

May combine two claims.

Because both polyanionic charge per unit volume and tissue hydration are constant between species regardless of PG composition, Meek and Leonard proposed a model in which fixed charges on GAGs are synthesised in proportion to total fibrillar collagen (types I and V); the larger the collagen fibrils, the greater the amount of fixed charge in the interfibrillar space, therefore the further apart the

“Because both polyanionic charge per unit volume and tissue hydration are constant between species, regardless of the PG composition (Scott and Bosworth, 1990, Gyi, 1988), they proposed a model in which the fixed charges on GAGs are synthesised in proportion to the total fibrillar collagen (types I and V) (Meek and Leonard, 1993); the larger the collagen fibrils, the greater amount of fixed charge”

• cites Scott and Bosworth, 1990 sourcePartly supported

  Split into 2 atoms — 0 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 1 unverifiable. Expand the claim to see per-atom verdicts.

  Experimental — accuracy not yet measured
• cites Gyi, 1988Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

• cites Meek and Leonard, 1993 sourceSupported

May combine two claims.

In corneal oedema (bullous keratopathy, Fuch's dystrophy), local decreases in refractive index are caused by pooling of fluid into lakes; the influx of fluid also disrupts fibril organisation and reduces destructive interference of scattered light.

“A similar effect occurs in corneal oedema (bullous keratopathy, Fuch's dystrophy) but in this case there are local decreases in refractive index caused by pooling of fluid into so-called “lakes” (Casadessus et al., 2012) (Fig. 8). The influx of fluid into the stroma also leads to disruption of the fibril organisation and thus to the reduction in destructive interference of scattered light.”

• cites Casadessus et al., 2012 sourcePartly supported

  Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  Experimental — accuracy not yet measured

May combine two claims.

The opacity of corneal scars is a result of improper remodelling of the connective tissue matrix; collagen fibrils are wider than normal and poorly ordered in scar tissue.

“On the other hand, the opacity of corneal scars is a result of improper remodelling of the connective tissue matrix; collagen fibrils are wider than normal and poorly ordered in scar tissue (Boote et al., 2013).”

• cites Boote et al., 2013 sourcePartly supported

  The Results (Collagen Spatial Organisation) report locally increased fibril diameter and reduced spatial order at the graft margins compared with unwounded corneas. The Discussion links these changes to incomplete remodelling and fibrotic scar tissue, but says they *could be a contributing factor* to visible opacity. The claim states a definite cause for corneal scars generally, beyond what the paper establishes for these graft margins. (LLM, conf=0.88)

  Experimental — accuracy not yet measured

May combine two claims.

Current work in our group has revealed that many elastic fibres seem to originate in the limbus, forming sheets at the edge of the cornea which then split up and extend as microfibrils, possibly oxytalan or elaunin, across the stroma.

“current work in our group has revealed that many fibres seem to originate in the limbus, forming sheets at the edge of the cornea which then split up and extend as microfibrils, possibly oxytalan or elaunin (Alexander and Garner, 1983), across the stroma (White et al., 2014).”

• cites White et al., 2014Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

May combine two claims.

In the human cornea, elastic fibres are present throughout most of the stromal depth but are concentrated below the posterior-most keratocyte layer.

“We have shown in the human cornea that these elastic fibres, though present throughout most of the stromal depth, are concentrated below the posterior-most keratocyte layer (unpublished results).”

Probably not a substantial claim: may not pass S3 (load-bearing).

Preliminary unpublished work by Knupp suggested there may be another type of 'attractive' force acting on the fibrils that would prevent them from drifting apart.

“Recent preliminary unpublished work by Knupp aimed at elucidating the role of keratocytes in corneal fibril deposition suggested that there may be another type of “attractive” force acting on the fibrils that would prevent them from drifting apart.”

The quote only partly states this claim.

In the same reconstructions, the distribution of distances between adjacent fibrils was narrow.

“What was evident, however, was that the distribution of distances between adjacent fibrils was narrow.”

May combine two claims.

The refractive index of the keratocyte cytoplasm matches that of the stroma as a whole, whereas upon activation the refractive index falls.

“Recent measurements from our group have shown that the refractive index of the keratocyte cytoplasm matches that of the stroma as a whole, whereas, upon activation, the refractive index falls.”

May combine two claims.

For two collagen fibrils, when the wavelength is smaller than the fibril separation, secondary radiation cancels completely in some directions and reinforces in others, so the resulting secondary waves exist only along distinct directions related to the fibril separation.

“This simple case shows that, if the wavelength is smaller than the fibril separation as depicted, there can be directions in which secondary radiation cancels out completely and others where they reinforce so that the resulting secondary waves exist only along distinct directions which are related to the fibril separation.”

Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

In a number of corneal pathologies, changes in one or more of the other layers can lead to increased light scattering and consequent loss of corneal transparency.

“in a number of corneal pathologies, changes in one or more of the other layers can lead to increased light scattering and consequent loss of corneal transparency”

Probably not a substantial claim: may not pass S3 (load-bearing).

The lamellae consist of narrow, parallel collagen fibrils embedded in a proteoglycan-rich hydrated matrix.

“The lamellae have long been known to consist of narrow, parallel collagen fibrils embedded in a proteoglycan-rich hydrated matrix.”

May combine two claims.

The elastic system may have an important biomechanical role but it is unlikely to influence transparency in the centre of the normal cornea.

“This elastic system may have an important biomechanical role but it is unlikely to influence transparency in the centre of the normal cornea.”

May combine two claims.

When a so-called big bubble is induced during pneumodissection, part of the posterior stroma often adheres to Descemet's membrane, indicating a natural cleavage plane in the stroma about 10 μm above Descemet's membrane.

“when a so-called “big bubble” is induced, part of the posterior stroma often adheres to the Descemet's membrane, and that there is, therefore, a natural cleavage plane in the stroma about 10 μm above Descemet's membrane (Jafarinasab et al., 2010, McKee et al., 2011).”

• cites Jafarinasab et al., 2010 sourceNot checked — no full text of the source
• cites McKee et al., 2011 sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing).

In humans, Bowman's layer and Descemet's membrane together contribute less than 4% to the total corneal thickness.

“in humans, Bowman's layer and Descemet's membrane, both collagenous tissues like the stroma, together contribute less than 4% to the total corneal thickness”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

The basic ultrastructure of the cornea had been described about 50 years ago and the principles behind corneal transparency were elucidated.

“About 50 years ago the basic ultrastructure had been described (Jakus, 1962) and the principles behind corneal transparency finally elucidated (Maurice, 1957, Hart and Farrell, 1969, Benedek, 1971)”

• cites Jakus, 1962Not checked — no full text of the source
• cites Maurice, 1957 sourceNot checked — no full text of the source
• cites Hart and Farrell, 1969 sourceNot checked — no full text of the source

May combine two claims.

The X-ray technique does not allow direct imaging of the lamellar structures; the arrangement of lamellae has to be inferred from the diffraction patterns.

“The X-ray technique does not allow direct imaging of the lamellar structures; the arrangement of lamellae has to be inferred from the diffraction patterns.”

May combine two claims.

Collagen crimp, in combination with elastic fibres in the peripheral cornea, may explain why this region is more pliable and absorbs intraocular pressure fluctuations, thus preventing deformation of the optically important central cornea.

“In fact, collagen crimp, in combination with elastic fibres in the peripheral cornea, may explain why this region is more pliable and absorbs intraocular pressure fluctuations (Boyce et al., 2008), thus preventing deformation of the optically important central cornea.”

• cites Boyce et al., 2008 sourceNot checked — no full text of the source

May combine two claims.

Collagen fibrils within the cornea are narrower than in many other connective tissues, and this is an important factor for transparency, which is a function of the diameter.

“Collagen fibrils within the cornea are narrower than in many other connective tissues and this is an important factor for transparency, which is a function of the diameter (Hart and Farrell, 1969).”

• cites Hart and Farrell, 1969 sourceNot checked — no full text of the source

May combine two claims.

There is a distribution of crimp angles in corneal collagen fibrils, which can be altered under mechanical load.

“There is a distribution of crimp angles, which can be altered under mechanical load.”

Classified as probably not a substantial claim. May combine two claims.

The basic principles of corneal structure and transparency have been known for some time, but recent X-ray scattering and other methods have revealed that the details of this structure are far more complex than previously thought.

“The basic principles of corneal structure and transparency have been known for some time, but in recent years X-ray scattering and other methods have revealed that the details of this structure are far more complex than previously thought”

Classified as probably not a substantial claim.

The tensile strength, defined shape, and optical clarity of the cornea may derive from the arrangement of the constituents of the stroma.

“For nearly a century it has been realised that these properties may derive from the arrangement of the constituents of the stroma (Eisler, 1930, Kolmer and Lauber, 1936).”

• cites Eisler, 1930 sourceNot checked — no full text of the source
• cites Kolmer and Lauber, 1936Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

May combine two claims.

Human corneal lamellae are typically up to 0.2 mm broad and 2 μm thick.

“These structures are of variable thickness, in humans typically up to 0.2 mm broad and 2 μm thick (Polack, 1961, Komai and Ushiki, 1991).”

• cites Polack, 1961 sourceNot checked — no full text of the source
• cites Komai and Ushiki, 1991Not checked — no full text of the source

May combine two claims.

X-ray data represent bulk averages throughout the tissue being sampled, so it is not possible to obtain information pertaining to adjacent lamellae using this approach.

“Furthermore, the X-ray data represent bulk averages throughout the tissue being sampled so, for instance, it is not possible to obtain information pertaining to adjacent lamellae using this approach.”

May combine two claims.

The molecules within a corneal collagen fibril are arranged axially with the typical 67 nm D-periodic stagger, with gaps between the N- and C-termini of consecutive molecules.

“which are arranged axially with the typical 67 nm D-periodic stagger (Meek and Holmes, 1983) with gaps between the N- and C-termini of consecutive molecules (Fig. 2).”

• cites Meek and Holmes, 1983 sourceNot checked — no full text of the source

May combine two claims.

The lamella arrangement within the cornea helps to maintain the overall shape of the tissue and is responsible for some optical properties such as corneal birefringence.

“The lamella arrangement within the cornea helps to maintain the overall shape of the tissue and is also responsible for some optical properties such as corneal birefringence.”

Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

In most mammals, the cornea is the only tissue requiring considerable tensile strength coupled with a perfectly defined shape and optical clarity.

“In most mammals, the cornea is the only tissue requiring considerable tensile strength coupled with a perfectly defined shape and optical clarity.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Modern technologies and theoretical modelling have started to explain how collagen fibrils are arranged within stromal lamellae and how proteoglycans maintain this ultrastructure.

“At the molecular level, modern technologies and theoretical modelling have started to explain exactly how the collagen fibrils are arranged within the stromal lamellae and how proteoglycans maintain this ultrastructure.”

May combine two claims.

The posterior lamellae in the central cornea are more hydrated and are believed to have less interlacing, lying on top of each other like the layers in plywood.

“The posterior lamellae in the central cornea are more hydrated and are believed to have less interlacing, lying on top of each other like the layers in plywood.”

May combine two claims.

The attractive forces are due to proteoglycans that connect two or more fibrils; these proteoglycans undergo thermally driven conformational changes so their glycosaminoglycan chains experience a force that prevents full extension and brings terminal ends and attached fibrils closer together, equivalent to molecular forces in a stretched rubber band.

“The attractive forces are due to those proteoglycans that connect two or more fibrils. These proteoglycans would be subject to thermally driven conformational changes so that their glycosaminoglycan chains will experience a force that prevents them from assuming a fully extended conformation and which brings their terminal ends, and the collagen fibrils attached to them, closer together. These”

• cites Feynman et al., 1963Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

May combine two claims.

A perfect hexagonal lattice is not required for corneal transparency; it is sufficient for the distance between adjacent fibrils to be constrained.

“As it turns out, the requirement of a perfect hexagonal lattice for the arrangement of the collagen fibrils is not a stringent one, in fact, to have a transparent cornea, it is sufficient for the distance between adjacent fibril to be constrained.”

May combine two claims.

Purified type I collagen forms fibrils of varying diameters in vitro, while type V collagen forms small fibrils.

“Both collagen types, when purified, could assemble in vitro to form fibrils, but in this case type I collagen formed fibrils of varying diameters, while type V formed small fibrils.”

• cites Birk et al., 1990 sourceNot checked — no full text of the source

Classified as probably not a substantial claim.

Stromal cells contain cytoplasmic molecules called corneal crystallins that act in much the same way as crystallins in the lens.

“They postulated that stromal cells contain cytoplasmic molecules called corneal crystallins that act in much the same was as crystallins in the lens.”

• cites Jester et al., 1999 sourceNot checked — no full text of the source
• cites Jester, 2008 sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

This suggests there may be another source of attractive forces between fibrils in the cornea which come from the pressure exerted by adjacent lamellae; fibrils at the interface between lamellae would be pushed inwards, creating a cascade effect that would hold all fibrils within any lamella close to each other.

“This suggested that there may be another source of attractive forces between fibrils in the cornea which come from the pressure exerted by the adjacent lamellae. In this case, the fibrils at the interface between lamellae would be pushed inwards, creating a cascade effect that ultimately would hold all fibrils within any lamella close to each other.”

May combine two claims.

Corneal collagen fibrils, as the principal load-bearing constituents of the lamellae, have to resist tensile forces due to intraocular pressure and protect inner ocular tissues from external trauma while remaining narrow to allow transparency; these are competing requirements.

“Corneal collagen fibrils, as the principal load-bearing constituents of the lamellae, have to resist the tensile forces due to the intraocular pressure and protect the inner ocular tissues from external trauma while at the same time remaining narrow to allow transparency of the tissue; these are competing requirements.”

Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

The normal adult human stroma contains four small leucine-rich proteoglycans: decorin, lumican, keratocan and mimecan.

“The normal adult human stroma contains four small leucine-rich proteoglycans: decorin, lumican, keratocan and mimecan.”

May combine two claims.

This idea is in agreement with the model of Cheng and Pinsky: if collagen fibrils were larger in diameter and the interfibrillar space was constant, the repulsive forces generated by the GAGs and their associated ions would be increased, which would increase swelling pressure and push the fibrils further apart to achieve equilibrium.

“This idea is in agreement with the model of Cheng and Pinsky (Fig. 11); if the collagen fibrils were larger in diameter and the interfibrillar space was constant, the repulsive forces generated by the GAGs and their associated ions would be increased, which would increase the swelling pressure and push the fibrils further apart in order to achieve equilibrium.”

May combine two claims.

The gel pressure that causes corneal swelling arises from net electrostatic charges within the stroma, most of which is contributed by the acidic groups of glycosaminoglycans, with another contribution from temporary complexing of free chloride ions to ligands within the stroma.

“The gel pressure that causes this swelling arises from net electrostatic charges within the stroma. Most of the electrostatic charge is contributed by the acidic groups of the glycosaminoglycans. The other contribution to net stromal charge arises from the temporary complexing of free chloride ions to ligands within the stroma (Hodson, 1997).”

• cites Hodson, 1997 sourceNot checked — no full text of the source

May combine two claims.

The distances between adjacent collagen fibrils are a consequence of the balancing of two opposing forces acting on the fibrils brought about by the proteoglycans; equilibrium distance is reached when attractive forces cancel repulsive forces.

“It was therefore proposed that the distances between adjacent collagen fibrils are a consequence of the balancing of two opposing forces acting on the fibrils brought about by the proteoglycans. In this model, both opposing forces depend on the separation between the fibrils, and the equilibrium distance between two fibrils is reached when the attractive forces between them cancel out the rep”

May combine two claims.

In real corneas, incoming light is scattered by many more fibrils than in the simulations, so the overall loss of intensity becomes significant and corneas with such structural defects exhibit impaired transparency.

“However, in real corneas, the incoming light is scattered by many more fibrils than those shown, so that the overall loss of intensity becomes significant and corneas with such structural defects exhibit impaired transparency.”

May combine two claims.

There are about 70 microfibrils within each corneal collagen fibril, tilted by about 15° to the fibril long axis, and this reduces the usual 67 nm axial periodicity seen in tendon and sclera to closer to 65 nm.

“There are about 70 microfibrils within each fibril (Holmes and Kadler, 2005) which are tilted by about 15° to the fibril long axis (Holmes et al., 2001) and this reduces the usual 67 nm axial periodicity seen in tendon and sclera, to closer to 65 nm (Meek et al., 1981, Marchini et al., 1986, Yamamoto et al., 2000).”

• cites Holmes and Kadler, 2005 sourceNot checked — no full text of the source
• cites Holmes et al., 2001 sourceNot checked — no full text of the source
• cites Meek et al., 1981 sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

The Cheng and Pinsky mechanism would also be relevant to corneal development and to the establishment of the stromal matrix.

“This mechanism would also be relevant to corneal development and to the establishment of the stromal matrix.”

May combine two claims.

Qualitative assessment of corneal transparency by laying the cornea on text or a grid is simple and quick but can be an extremely insensitive test.

“This technique may be useful for comparative purposes as it is simple and quick, and we have used it ourselves (Mi et al., 2011). However, Maurice (2001) pointed out that this can be an extremely insensitive test”

• cites Maurice, 2001Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim: may not pass S3 (load-bearing).

Many other microscopical techniques reveal the presence of this microfibrillar substructure within corneal collagen fibrils.

“Many other microscopical techniques also reveal the presence of this microfibrillar substructure within corneal collagen fibrils (Meek, 2009).”

• cites Meek, 2009Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim: may not pass S3 (load-bearing).

The general consensus was that the cornea needed to be optically homogenous to be transparent.

“The transparency of the corneal stroma has been studied since the nineteenth century and the general consensus was that the cornea needed to be optically homogenous to be transparent (Schweigger-Seidel, 1869, Von Fleischl, 1880, Ranvier, 1898).”

• cites Schweigger-Seidel, 1869Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

• cites Von Fleischl, 1880Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

• cites Ranvier, 1898Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

May combine two claims.

This dynamic proteoglycan connection model would endow the whole cornea with a less rigid and more fluid overall structure, making it more resilient to deformations and facilitating transport of molecules and nutrients across the cornea.

“This would endow the whole cornea with a less rigid and more fluid overall structure which would make the cornea more resilient to deformations due to external stresses and would facilitate the transport of molecules and nutrients across the cornea.”

May combine two claims.

Opacities associated with corneal dystrophies (granular, lattice, macular, Schnyder) are caused mostly by different kinds of stromal deposits; such deposits cause local changes in refractive index, and these refractive index discontinuities, if comparable with the wavelength of light, lead to increased light scatter.

“Opacities associated with corneal dystrophies (granular dystrophy, lattice dystrophy, macular dystrophy, Schnyder dystrophy) are caused mostly by different kinds of stromal deposits. Such deposits cause local changes in the refractive index of the stroma, and these refractive index discontinuities, if comparable with the wavelength of light, lead to increased light scatter.”

May combine two claims.

At the supra-molecular level, the initial building block is a 4-8 nm wide microfibril with a left-handed twist of the constituent molecules.

“At the supra-molecular level, the initial building block is a 4–8 nm wide microfibril (Baldock et al., 2002) with a left-handed twist of the constituent molecules (Fig. 2).”

• cites Baldock et al., 2002 sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Biglycan (containing dermatan sulphate) and fibromodulin (containing keratan sulphate) are two other proteoglycans associated with the cornea.

“Two other proteoglycans associated with the cornea are biglycan (containing dermatan sulphate) and fibromodulin (containing keratan sulphate).”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Models by Maurice (1962) and Hart and Farrell (1969) proposed that collagen fibrils in the corneal stroma are connected to six adjacent fibrils by proteoglycans at regular axial intervals, and that the defined lengths of the proteoglycans force the fibrils onto a perfect hexagonal lattice, guaranteeing corneal transparency.

“The models they proposed were based essentially on the collagen fibrils in the corneal stroma being connected to six adjacent fibrils by proteoglycans at regular axial intervals. The defined lengths of the proteoglycans would force the fibrils on a perfect hexagonal lattice, which would guarantee corneal transparency.”

• cites Maurice in 1962 sourceNot checked — no full text of the source
• cites Hart and Farrell in 1969 sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Decorin contains dermatan sulphate and chondroitin sulphate, while lumican, keratocan and mimecan contain keratan sulphate GAGs.

“The first contains dermatan sulphate and chondroitin sulphate, while the final three contain keratan sulphate GAGs.”

May combine two claims.

Boettner and Wolter (1962) found that corneal transmittance rose rapidly from 300 nm, reaching 80% at 380 nm and more than 90% between 500 nm and 1300 nm.

“Boettner and Wolter (1962) found that the corneal transmittance rose rapidly from 300 nm, reaching 80% at 380 nm and more than 90% between 500 nm and 1300 nm.”

• cites Boettner and Wolter, 1962Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

May combine two claims.

Corneal collagen fibrils have surface dips or grooves in the gap zone compared to the overlap zone, explained by the 4:5 ratio of molecular density in the two zones.

“It appears that fibrils have surface dips or grooves in the gap zone compared to the overlap zone, explained by the 4:5 ratio of molecular density in the two zones.”

Probably not a substantial claim: may not pass S3 (load-bearing).

The suggestion that collagen fibrils needed to have the same refractive index as their surroundings was stated specifically by Renault (1889).

“The suggestion that collagen fibrils needed to have the same refractive index as their surroundings was stated specifically by Renault (1889).”

• cites Renault, 1889Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

May combine two claims.

Two of the most important structural factors for corneal transparency are the uniformity of the diameters of the collagen fibrils and the restriction in the range of distances between adjacent collagen fibrils.

“Two of the most important structural factors for corneal transparency are the uniformity of the diameters of the collagen fibrils, and the restriction in the range of distances between adjacent collagen fibrils.”

May combine two claims.

Corneal opacity during corneal wound healing, or transitory haze following refractive surgery or corneal cross-linking, is caused by activated corneal keratocytes; once activated, these cells have a lower refractive index than the surrounding connective tissue.

“Corneal opacity during corneal wound healing, or transitory haze following refractive surgery or corneal cross-linking, is caused by activated corneal keratocytes (Connon et al., 2003, Moller-Pedersen, 2004). Once activated, these cells have a lower refractive index than the surrounding connective tissue.”

• cites Connon et al., 2003 sourceNot checked — no full text of the source
• cites Moller-Pedersen, 2004 sourceNot checked — no full text of the source

May combine two claims.

Any change in cytoplasmic content when keratocytes transform to myofibroblasts is likely to alter the refractive index, and this would contribute to the increase in light scatter.

“Any change in cytoplasmic content when the keratocytes transform to myofibroblasts is likely to alter the refractive index, and this would then contribute to the increase in light scatter.”

May combine two claims.

Corneal fibrils are a blend of type I and type V collagens, and the collagen V to collagen I ratio is noticeably higher in corneal stroma than in other tissues.

“It was found that corneal fibrils were a blend of type I and type V collagens, but unlike in other tissues, the collagen V to collagen I ratio was noticeably higher in corneal stroma (Birk et al., 1990).”

• cites Birk et al., 1990 sourceNot checked — no full text of the source

The quote only partly states this claim.

A fibrillar arrangement with short range order, where any two fibrils cannot be closer than 62 nm, is essential to corneal transparency.

“This type of fibrillar arrangement is said to possess short range order and this property is essential to corneal transparency.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Biglycan occurs in the epithelium and in the stroma of some pathological corneas.

“Biglycan occurs in the epithelium and in the stroma of some pathological corneas (Funderburgh et al., 1998)”

• cites Funderburgh et al., 1998Not checked — no full text of the source

May combine two claims.

The presence of oversized collagen fibrils, probably formed by fibril fusion, is also a major cause of corneal light scatter seen in many mucopolysaccharidoses, though accompanying deposition of stored proteoglycans with cells or within the matrix also contributes.

“The presence of similar oversized collagen fibrils, probably formed by fibril fusion (Fig. 7), is also a major cause of corneal light scatter seen in many of the mucopolysaccharidoses, though there is often accompanying deposition of stored proteoglycans with cells or within the matrix that also contributes.”

May combine two claims.

Haze or opacity within the cornea can have multiple causes, and it is often incorrect to attribute the light scattering to a single structural change that may be observed within the tissue.

“Thus haze or opacity within the cornea can have multiple causes, and it is often incorrect to attribute the light scattering to a single structural change that may be observed within the tissue.”