Retinal Laminar Architecture in Human Retinitis Pigmentosa Caused by Rhodopsin Gene Mutations
Open accessAbstract
PURPOSE: To determine the underlying retinal micropathology in subclasses of autosomal dominant retinitis pigmentosa (ADRP) caused by rhodopsin (RHO) mutations. METHODS: Patients with RHO-ADRP (n = 17, ages 6-73 years), representing class A (R135W and P347L) and class B (P23H, T58R, and G106R) functional phenotypes, were studied with optical coherence tomography (OCT), and colocalized visual thresholds were determined by dark- and light-adapted chromatic perimetry. Autofluorescence imaging was performed with near-infrared light. Retinal histology in hT17M-rhodopsin mice was compared with the human results. RESULTS: Class A patients had only cone-mediated vision. The outer nuclear layer (ONL) thinned with eccentricity and was not detectable within 3 to 4 mm of the fovea. Scotomatous extracentral retina showed loss of ONL, thickening of the inner retina, and demelanization of RPE. Class B patients had superior-inferior asymmetry in function and structure. The superior retina could have normal rod and cone vision, normal lamination (including ONL) and autofluorescence of the RPE melanin; laminopathy was found in the scotomas. With Fourier-domain-OCT, there was apparent inner nuclear layer (INL) thickening in regions with ONL thinning. Retinal regions without ONL had a thick hyporeflective layer that was continuous with the INL from neighboring regions with normal lamination. Transgenic mice had many of the laminar abnormalities found in patients. CONCLUSIONS: Retinal laminar abnormalities were present in both classes of RHO-ADRP and were related to the severity of colocalized vision loss. The results in human class B and the transgenic mice support the following disease sequence: ONL diminution with INL thickening; amalgamation of residual ONL with the thickened INL; and progressive retinal remodeling with eventual thinning.
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Subretinal delivery is limited to tissues in contact with the bleb(s).
“delivery is limited to tissues in contact with the bleb(s),18–20”
From Antibody neutralization poses a barrier to intravitreal adeno-associated viral vector gene delivery to non-human primates (2015) · cites this paper as [18]
The Discussion addresses which retinal regions might be treatable in RHO-associated retinitis pigmentosa, but it does not describe a delivery area defined by a subretinal bleb. Searches for “bleb,” “subretinal,” and delivery limited to tissues in contact with a bleb found no passage supporting the claim; the available passages have no page labels. (LLM, conf=0.76)
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- Authors
- Aleman, T. S., Cideciyan, A. V., Sumaroka, A., Windsor, E. A. M., Herrera, W., White, D. A., Kaushal, S., Naidu, A., Roman, A. J., Schwartz, S. B., Stone, E. M., & Jacobson, S. G.
- Affiliations
- From the Scheie Eye Institute, Department of Ophthalmology, University of Pennsylvania, Philadelphia, Pennsylvania; the
- University of Pennsylvania (US)
- University of Florida (US)
- University of Iowa (US)
- Venue
- Investigative Opthalmology & Visual Science
- Published
- 2008-04-01
- Volume
- 49
- Issue
- 4
- Pages
- 1580
- ISSN
- 0146-0404 (ISSN-L)
- 1552-5783
- PMC
- PMC3179264
- OpenAlex
- W1968155207
- Cited by
- 133
- References
- 64
- Citations by year
- 2026: 2 · 2025: 8 · 2024: 3 · 2023: 5 · 2022: 7 · 2021: 12 · 2020: 4 · 2019: 5 · 2018: 5 · 2017: 5 · 2016: 8 · 2015: 6 · 2014: 9 · 2013: 9 · 2012: 9
- FWCI
- 4.94
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- public-domain
- Locations
- Investigative Ophthalmology & Visual Science (publishedVersion, public-domain)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Foundation Fighting Blindness
- Research to Prevent Blindness
- Macula Vision Research Foundation
- Hope For Vision
- Alcon Research Institute
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and Kidney Cyst Diseases
- Keywords
- autosomal dominant retinitis pigmentosa, rhodopsin mutations, outer nuclear layer thinning, retinal remodeling, scotoma, retinal histopathology
- MeSH terms
- Adolescent, Adult, Aged, Animals, Child, Child, Preschool, Dark Adaptation, Electroretinography, Female, Fluorescence, Genes, Dominant, Humans, Male, Mice, Transgenic, Middle Aged, Mutation, Retina, Retinitis Pigmentosa, Rhodopsin, Sensory Thresholds, Vision Disorders, Visual Fields, Tomography, Optical Coherence, Mice, Visual Field Tests
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