The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.
Diabetic Retinopathy: Pathophysiology and Treatments
Open accessAbstract
Diabetic retinopathy (DR) is the most common complication of diabetes mellitus (DM). It has long been recognized as a microvascular disease. The diagnosis of DR relies on the detection of microvascular lesions. The treatment of DR remains challenging. The advent of anti-vascular endothelial growth factor (VEGF) therapy demonstrated remarkable clinical benefits in DR patients; however, the majority of patients failed to achieve clinically-significant visual improvement. Therefore, there is an urgent need for the development of new treatments. Laboratory and clinical evidence showed that in addition to microvascular changes, inflammation and retinal neurodegeneration may contribute to diabetic retinal damage in the early stages of DR. Further investigation of the underlying molecular mechanisms may provide targets for the development of new early interventions. Here, we present a review of the current understanding and new insights into pathophysiology in DR, as well as clinical treatments for DR patients. Recent laboratory findings and related clinical trials are also reviewed.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Treatment Techniques and Clinical Guidelines for Photocoagulation of Diabetic Macular Edema
(1987) · Ophthalmology · doi:10.1016/s0161-6420(87)33527-4 · Cited by 544
Research works printed but not linked: 76
- Verges, 2016, Diabetic macular edema pathophysiology: Vasogenic versus inflammatory, J. Diabetes Res., 2016, 2156273
- Gonzalez, 2016, Early and long-term responses to anti-vascular endothelial growth factor therapy in diabetic macular edema: Analysis of protocol I data, Am. J. Ophthalmol., 172, 72, 10.1016/j.ajo.2016.09.012 · DOI · Paper page
- Brownlee, 2005, The pathobiology of diabetic complications: A unifying mechanism, Diabetes, 54, 1615, 10.2337/diabetes.54.6.1615 · DOI · Paper page
- Bek, 2017, Diameter changes of retinal vessels in diabetic retinopathy, Curr. Diabetes Rep., 17, 82, 10.1007/s11892-017-0909-9 · DOI
- Naruse, 2000, Aldose reductase inhibition prevents glucose-induced apoptosis in cultured bovine retinal microvascular pericytes, Exp. Eye Res., 71, 309, 10.1006/exer.2000.0882 · DOI
- Romeo, 2002, Activation of nuclear factor-kappaB induced by diabetes and high glucose regulates a proapoptotic program in retinal pericytes, Diabetes, 51, 2241, 10.2337/diabetes.51.7.2241 · DOI · Paper page
- Ejaz, 2008, Importance of pericytes and mechanisms of pericyte loss during diabetes retinopathy, Diabetes Obes. Metab., 10, 53, 10.1111/j.1463-1326.2007.00795.x · DOI · Paper page
- Beltramo, 2013, Pericyte loss in diabetic retinopathy: Mechanisms and consequences, Curr. Med. Chem., 20, 3218, 10.2174/09298673113209990022 · DOI · Paper page
- Huang, 2015, Deletion of placental growth factor prevents diabetic retinopathy and is associated with Akt activation and HIF1alpha-VEGF pathway inhibition, Diabetes, 64, 200, 10.2337/db14-0016 · DOI
- Lupo, 2013, Role of phospholipases A2 in diabetic retinopathy: In vitro and in vivo studies, Biochem. Pharmacol., 86, 1603, 10.1016/j.bcp.2013.09.008 · doi:10.1016/j.bcp.2013.09.008
- Antonetti, 1999, Vascular endothelial growth factor induces rapid phosphorylation of tight junction proteins occludin and zonula occluden 1. A potential mechanism for vascular permeability in diabetic retinopathy and tumors, J. Biol. Chem., 274, 23463, 10.1074/jbc.274.33.23463 · DOI · Paper page
- Rousseau, 1997, p38 MAP kinase activation by vascular endothelial growth factor mediates actin reorganization and cell migration in human endothelial cells, Oncogene, 15, 2169, 10.1038/sj.onc.1201380 · DOI · Paper page
- Li, 2010, Inhibition of reactive oxygen species by Lovastatin downregulates vascular endothelial growth factor expression and ameliorates blood-retinal barrier breakdown in db/db mice: Role of nadph oxidase 4, Diabetes, 59, 1528, 10.2337/db09-1057 · DOI
- Aiello, 1994, Vascular endothelial growth factor in ocular fluid of patients with diabetic retinopathy and other retinal disorders, N. Engl. J. Med., 331, 1480, 10.1056/NEJM199412013312203 · DOI · Paper page
- Adamis, 1994, Increased vascular endothelial growth factor levels in the vitreous of eyes with proliferative diabetic retinopathy, Am. J. Ophthalmol., 118, 445, 10.1016/S0002-9394(14)75794-0 · DOI · Paper page
- Patel, 2005, Angiopoietin concentrations in diabetic retinopathy, Br. J. Ophthalmol., 89, 480, 10.1136/bjo.2004.049940 · DOI
- Rangasamy, 2011, A potential role for angiopoietin 2 in the regulation of the blood-retinal barrier in diabetic retinopathy, Investig. Ophthalmol. Vis. Sci., 52, 3784, 10.1167/iovs.10-6386 · DOI · Paper page
- Miyamoto, 1999, Prevention of leukostasis and vascular leakage in streptozotocin-induced diabetic retinopathy via intercellular adhesion molecule-1 inhibition, Proc. Natl. Acad. Sci. USA, 96, 10836, 10.1073/pnas.96.19.10836 · DOI · Paper page
- Yuuki, 2001, Inflammatory cytokines in vitreous fluid and serum of patients with diabetic vitreoretinopathy, J. Diabetes Its Complicat., 15, 257, 10.1016/S1056-8727(01)00155-6 · DOI
- Schroder, 1991, Activated monocytes and granulocytes, capillary nonperfusion, and neovascularization in diabetic retinopathy, Am. J. Pathol., 139, 81
- Miyamoto, 1998, In vivo demonstration of increased leukocyte entrapment in retinal microcirculation of diabetic rats, Investig. Ophthalmol. Vis. Sci., 39, 2190
- Joussen, 2003, Suppression of Fas-FasL-induced endothelial cell apoptosis prevents diabetic blood-retinal barrier breakdown in a model of streptozotocin-induced diabetes, FASEB J., 17, 76, 10.1096/fj.02-0157fje · DOI · Paper page
- Barouch, 2000, Integrin-mediated neutrophil adhesion and retinal leukostasis in diabetes, Investig. Ophthalmol. Vis. Sci., 41, 1153
- Chibber, 2000, Activity of the glycosylating enzyme, core 2 GlcNAc (beta1,6) transferase, is higher in polymorphonuclear leukocytes from diabetic patients compared with age-matched control subjects: Relevance to capillary occlusion in diabetic retinopathy, Diabetes, 49, 1724, 10.2337/diabetes.49.10.1724 · DOI
- Kasza, 2017, Plasma E-selectin levels can play a role in the development of diabetic retinopathy, Graefe’s Arch. Clin. Exp. Ophthalmol., 255, 25, 10.1007/s00417-016-3411-1 · doi:10.1007/s00417-016-3411-1
- Limb, 1999, Vascular adhesion molecules in vitreous from eyes with proliferative diabetic retinopathy, Investig. Ophthalmol. Vis. Sci., 40, 2453
- Joussen, 2004, A central role for inflammation in the pathogenesis of diabetic retinopathy, FASEB J., 18, 1450, 10.1096/fj.03-1476fje · DOI · Paper page
- Suzuki, 2011, Expression profiles of cytokines and chemokines in vitreous fluid in diabetic retinopathy and central retinal vein occlusion, Jpn. J. Ophthalmol., 55, 256, 10.1007/s10384-011-0004-8 · DOI
- Rangasamy, S., McGuire, P.G., Franco Nitta, C., Monickaraj, F., Oruganti, S.R., and Das, A. (2014). Chemokine mediated monocyte trafficking into the retina: Role of inflammation in alteration of the blood-retinal barrier in diabetic retinopathy. PLoS ONE, 9. · DOI · Paper page
- Sivkova, 2011, Serum inflammatory cytokines IL-1beta, IL-6, TNF-alpha and VEGF have influence on the development of diabetic retinopathy, Folia Med., 53, 44
- Boss, 2017, Assessment of neurotrophins and inflammatory mediators in vitreous of patients with diabetic retinopathy, Investig. Ophthalmol. Vis. Sci., 58, 5594, 10.1167/iovs.17-21973 · DOI · Paper page
- Abcouwer, 2017, Muller cell-microglia cross talk drives neuroinflammation in diabetic retinopathy, Diabetes, 66, 261, 10.2337/dbi16-0047 · doi:10.2337/dbi16-0047
- Sorrentino, 2016, The importance of glial cells in the homeostasis of the retinal microenvironment and their pivotal role in the course of diabetic retinopathy, Life Sci., 162, 54, 10.1016/j.lfs.2016.08.001 · DOI
- Barber, 1998, Neural apoptosis in the retina during experimental and human diabetes. Early onset and effect of insulin, J. Clin. Investig., 102, 783, 10.1172/JCI2425 · DOI · Paper page
- Kowluru, 2002, Diabetes-induced activation of caspase-3 in retina: Effect of antioxidant therapy, Free Radic. Res., 36, 993, 10.1080/1071576021000006572 · DOI
- Podesta, 2000, Bax is increased in the retina of diabetic subjects and is associated with pericyte apoptosis in vivo and in vitro, Am. J. Pathol., 156, 1025, 10.1016/S0002-9440(10)64970-X · DOI · Paper page
- Dralands, 2004, Expression of apoptosis markers in the retinas of human subjects with diabetes, Investig. Ophthalmol. Vis. Sci., 45, 2760, 10.1167/iovs.03-1392 · DOI · Paper page
- Tien, 2017, High glucose induces mitochondrial dysfunction in retinal muller cells: Implications for diabetic retinopathy, Investig. Ophthalmol. Vis. Sci., 58, 2915, 10.1167/iovs.16-21355 · DOI
- Sasaki, 2010, Neurodegenerative influence of oxidative stress in the retina of a murine model of diabetes, Diabetologia, 53, 971, 10.1007/s00125-009-1655-6 · DOI · Paper page
- Sohn, 2016, Retinal neurodegeneration may precede microvascular changes characteristic of diabetic retinopathy in diabetes mellitus, Proc. Natl. Acad. Sci. USA, 113, E2655, 10.1073/pnas.1522014113 · DOI · Paper page
- Kok, 2009, Selective loss of inner retinal layer thickness in type 1 diabetic patients with minimal diabetic retinopathy, Investig. Ophthalmol. Vis. Sci., 50, 3404, 10.1167/iovs.08-3143 · DOI · Paper page
- Mitchell, 2011, The restore study: Ranibizumab monotherapy or combined with laser versus laser monotherapy for diabetic macular edema, Ophthalmology, 118, 615, 10.1016/j.ophtha.2011.01.031 · DOI · Paper page
- Massin, 2010, Safety and efficacy of ranibizumab in diabetic macular edema (resolve study): A 12-month, randomized, controlled, double-masked, multicenter phase ii study, Diabetes Care, 33, 2399, 10.2337/dc10-0493 · DOI · Paper page
- Heier, 2016, Intravitreal aflibercept for diabetic macular edema: 148-week results from the vista and vivid studies, Ophthalmology, 123, 2376, 10.1016/j.ophtha.2016.07.032 · DOI · Paper page
- Writing Committee for the Diabetic Retinopathy Clinical Research Network, Gross, J.G., Glassman, A.R., Jampol, L.M., Inusah, S., Aiello, L.P., Antoszyk, A.N., Baker, C.W., Berger, B.B., and Bressler, N.M. (2015). Panretinal photocoagulation vs intravitreous ranibizumab for proliferative diabetic retinopathy: A randomized clinical trial. JAMA, 314, 2137–2146. · DOI · Paper page
- Sivaprasad, 2017, Clinical efficacy of intravitreal aflibercept versus panretinal photocoagulation for best corrected visual acuity in patients with proliferative diabetic retinopathy at 52 weeks (CLARITY): A multicentre, single-blinded, randomised, controlled, phase 2b, non-inferiority trial, Lancet, 389, 2193, 10.1016/S0140-6736(17)31193-5 · DOI · Paper page
- Diabetic Retinopathy Clinical Research Network, Wells, J.A., Glassman, A.R., Ayala, A.R., Jampol, L.M., Aiello, L.P., Antoszyk, A.N., Arnold-Bush, B., Baker, C.W., and Bressler, N.M. (2015). Aflibercept, bevacizumab, or ranibizumab for diabetic macular edema. N. Engl. J. Med., 372, 1193–1203. · DOI · Paper page
- Diabetic Retinopathy Clinical Research Network, Elman, M.J., Aiello, L.P., Beck, R.W., Bressler, N.M., Bressler, S.B., Edwards, A.R., Ferris, F.L., Friedman, S.M., and Glassman, A.R. (2010). Randomized trial evaluating ranibizumab plus prompt or deferred laser or triamcinolone plus prompt laser for diabetic macular edema. Ophthalmology, 117, 1064–1077e.35. · DOI · Paper page
- Kurihara, 2012, Targeted deletion of vegfa in adult mice induces vision loss, J. Clin. Investig., 122, 4213, 10.1172/JCI65157 · DOI · Paper page
- Wroblewski, 2016, Topical squalamine 0.2% and intravitreal ranibizumab 0.5 mg as combination therapy for macular edema due to branch and central retinal vein occlusion: An open-label, randomized study, Ophthalmic Surg. Lasers Imag. Retina, 47, 914, 10.3928/23258160-20161004-04 · doi:10.3928/23258160-20161004-04
- Campochiaro, 2016, Enhanced benefit in diabetic macular edema from AKB-9778 Tie2 activation combined with vascular endothelial growth factor suppression, Ophthalmology, 123, 1722, 10.1016/j.ophtha.2016.04.025 · DOI
- Sultan, 2011, A phase 2/3, multicenter, randomized, double-masked, 2-year trial of pegaptanib sodium for the treatment of diabetic macular edema, Ophthalmology, 118, 1107, 10.1016/j.ophtha.2011.02.045 · DOI · Paper page
- Lattanzio, 2017, Intravitreal steroids in diabetic macular edema, Dev. Ophthalmol., 60, 78, 10.1159/000459691 · DOI
- Boyer, 2014, Three-year, randomized, sham-controlled trial of dexamethasone intravitreal implant in patients with diabetic macular edema, Ophthalmology, 121, 1904, 10.1016/j.ophtha.2014.04.024 · DOI · Paper page
- Pacella, 2016, An eighteen-month follow-up study on the effects of intravitreal dexamethasone implant in diabetic macular edema refractory to anti-VEGF therapy, Int. J. Ophthalmol., 9, 1427
- Campochiaro, 2011, Long-term benefit of sustained-delivery fluocinolone acetonide vitreous inserts for diabetic macular edema, Ophthalmology, 118, 626, 10.1016/j.ophtha.2010.12.028 · DOI · Paper page
- Pacella, 2016, Management of anterior chamber dislocation of a dexamethasone intravitreal implant: A case report, J. Med. Case Rep., 10, 282, 10.1186/s13256-016-1077-2 · doi:10.1186/s13256-016-1077-2
- Pearson, 2011, Fluocinolone acetonide intravitreal implant for diabetic macular edema: A 3-year multicenter, randomized, controlled clinical trial, Ophthalmology, 118, 1580, 10.1016/j.ophtha.2011.02.048 · DOI · Paper page
- Arnarsson, 2000, Laser treatment and the mechanism of edema reduction in branch retinal vein occlusion, Investig. Ophthalmol. Vis. Sci., 41, 877
- Ogata, 2001, Upregulation of pigment epithelium-derived factor after laser photocoagulation, Am. J. Ophthalmol., 132, 427, 10.1016/S0002-9394(01)01021-2 · doi:10.1016/s0002-9394(01)01021-2
- Fong, 2007, Visual side effects of successful scatter laser photocoagulation surgery for proliferative diabetic retinopathy: A literature review, Retina, 27, 816, 10.1097/IAE.0b013e318042d32c · DOI · Paper page
- Distefano, 2017, Combination of anti-VEGF and laser photocoagulation for diabetic macular edema: A review, J. Ophthalmol., 2017, 2407037, 10.1155/2017/2407037 · DOI
- Blumenkranz, 2006, Semiautomated patterned scanning laser for retinal photocoagulation, Retina, 26, 370, 10.1097/00006982-200603000-00024 · DOI · Paper page
- Vujosevic, 2013, Subthreshold laser therapy for diabetic macular edema: Metabolic and safety issues, Curr. Med. Chem., 20, 3267, 10.2174/09298673113209990030 · doi:10.2174/09298673113209990030
- Neubauer, 2013, Navigated macular laser decreases retreatment rate for diabetic macular edema: A comparison with conventional macular laser, Clin. Ophthalmol., 7, 121
- Paradies, 2009, Role of cardiolipin peroxidation and Ca2+ in mitochondrial dysfunction and disease, Cell Calcium, 45, 643, 10.1016/j.ceca.2009.03.012 · DOI · Paper page
- Alam, 2015, A mitochondrial therapeutic reverses visual decline in mouse models of diabetes, Dis. Models Mechan., 8, 701
- Gebka, 2014, Effect of the administration of alpha-lipoic acid on contrast sensitivity in patients with type 1 and type 2 diabetes, Mediat. Inflamm., 2014, 131538, 10.1155/2014/131538 · DOI
- Moschos, 2017, Effect of carotenoids dietary supplementation on macular function in diabetic patients, Eye Vis., 4, 23, 10.1186/s40662-017-0088-4 · DOI
- Kan, 2017, Effects of alpha-lipoic acid on retinal ganglion cells, retinal thicknesses, and VEGF production in an experimental model of diabetes, Int. Ophthalmol., 37, 1269, 10.1007/s10792-016-0396-z · DOI
- Li, 2009, Effect of lutein on retinal neurons and oxidative stress in a model of acute retinal ischemia/reperfusion, Investig. Ophthalmol. Vis. Sci., 50, 836, 10.1167/iovs.08-2310 · DOI
- Li, 2012, Anti-inflammatory effects of lutein in retinal ischemic/hypoxic injury: In vivo and in vitro studies, Investig. Ophthalmol. Vis. Sci., 53, 5976, 10.1167/iovs.12-10007 · DOI
- Muriach, 2006, Lutein effect on retina and hippocampus of diabetic mice, Free Radic. Biol. Med., 41, 979, 10.1016/j.freeradbiomed.2006.06.023 · DOI
- McVicar, 2011, Intervention with an erythropoietin-derived peptide protects against neuroglial and vascular degeneration during diabetic retinopathy, Diabetes, 60, 2995, 10.2337/db11-0026 · DOI
- Canning, 2016, Lipoprotein-associated phospholipase A2 (Lp-PLA2) as a therapeutic target to prevent retinal vasopermeability during diabetes, Proc. Natl. Acad. Sci. USA, 113, 7213, 10.1073/pnas.1514213113 · DOI
- Staurenghi, 2015, Darapladib, a lipoprotein-associated phospholipase A2 inhibitor, in diabetic macular edema: A 3-month placebo-controlled study, Ophthalmology, 122, 990, 10.1016/j.ophtha.2014.12.014 · DOI
Cited by
Xu, G.-T., Zhang, J.-F., & Tang, L. (2023) · Neural Regeneration Research · doi:10.4103/1673-5374.355743 · Cited by 280
Regulation of blood-retinal barrier cell-junctions in diabetic retinopathy
Rudraraju, M., Narayanan, S. P., & Somanath, P. R. (2020) · Pharmacological Research · doi:10.1016/j.phrs.2020.105115 · Cited by 217
The Angiotensin AT2 Receptor: From a Binding Site to a Novel Therapeutic Target
Steckelings, U. M., Widdop, R. E., Sturrock, E. D., Lubbe, L., Hussain, T., Kaschina, E., Unger, T., Hallberg, A., Carey, R. M., & Sumners, C. (2022) · Pharmacological Reviews · doi:10.1124/pharmrev.120.000281 · Cited by 97
Gelfman, C. M., Grishanin, R., Bender, K. O., Nguyen, A., Greengard, J., Sharma, P., Nieves, J., Kiss, S., & Gasmi, M. (2021) · Journal of Ocular Pharmacology and Therapeutics · doi:10.1089/jop.2021.0001 · Cited by 55
Shi, J., Lv, H., Tang, C., Li, Y., Huang, J., & Zhang, H. (2021) · Molecular Medicine Reports · doi:10.3892/mmr.2021.12112 · Cited by 34
Metadata
- Authors
- Wang, W., & Lo, A. C. Y.
- Venue
- International Journal of Molecular Sciences
- Publisher
- MDPI AG
- Published
- 2018-06-20
- Volume
- 19
- Issue
- 6
- Pages
- 1816
- ISSN
- 1422-0067 (ISSN-L)
- OpenAlex
- W2809489644
- Cited by
- 1,358
- References
- 1
- FWCI
- 64.51
- Type
- journal article
- Language
- en
- Open access
- gold
- Funders
- Health and Medical Research Fund (04150746)
- The University of Hong Kong Seed Funding Programme for Basic Research (201310159038)
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
How to cite
Cite CoChat for the checks on this page, and the paper for its own findings.
- This page
- CoChat. (2026). Citation check: Diabetic Retinopathy: Pathophysiology and Treatments. https://app.cochat.ai/papers/10.3390/ijms19061816
- The paper
- Wang, W., & Lo, A. C. Y. (2018). Diabetic Retinopathy: Pathophysiology and Treatments. International Journal of Molecular Sciences. https://doi.org/10.3390/ijms19061816
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.