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Retinal laminar architecture in human retinitis pigmentosa caused by Rhodopsin gene mutations
Journal article   Open access   Peer reviewed

Retinal laminar architecture in human retinitis pigmentosa caused by Rhodopsin gene mutations

Tomas S Aleman, Artur V Cideciyan, Alexander Sumaroka, Elizabeth A M Windsor, Waldo Herrera, D Alan White, Shalesh Kaushal, Anjani Naidu, Alejandro J Roman, Sharon B Schwartz, …
Investigative ophthalmology & visual science, Vol.49(4), pp.1580-1591
04/2008
DOI: 10.1167/iovs.07-1110
PMCID: PMC3179264
PMID: 18385078
url
https://doi.org/10.1167/iovs.07-1110View
Published (Version of record) Open Access

Abstract

To determine the underlying retinal micropathology in subclasses of autosomal dominant retinitis pigmentosa (ADRP) caused by rhodopsin (RHO) mutations. 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. 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. 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.
Fluorescence Mutation Visual Fields - physiology Humans Middle Aged Child, Preschool Male Dark Adaptation Vision Disorders - physiopathology Genes, Dominant Adult Female Child Retinitis Pigmentosa - physiopathology Electroretinography Tomography, Optical Coherence Retinitis Pigmentosa - genetics Mice, Transgenic Retinitis Pigmentosa - diagnosis Animals Rhodopsin - genetics Sensory Thresholds - physiology Adolescent Aged Mice Visual Field Tests Retina - pathology

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