Retinal Remodeling in Human Retinitis Pigmentosa Caused by Rhodopsin Gene Mutations: Intraretinal and Inter-Class Differences

Abstract

Purpose:: To increase our understanding of the pathogenic sequence in retinitis pigmentosa (RP) caused by rhodopsin (RHO) mutations.

Methods:: RHO mutations representing two different classes of disease expression (Cideciyan et al., 1998; PNAS 95:7103) were included. Class A disease shows severely abnormal rod function across the retina from early life; Class B disease can have normal rods even into adult life and topographical variation in severity. In-vivo retinal structure was studied by optical coherence tomography (OCT) along the vertical meridian and related to visual thresholds. Three major features of OCTs were considered: (a) inner retina (ILM to OPL), (b) photoreceptor nuclear layer (ONL), and (c) photoreceptor segments (ELM to RPE).

Results:: Class B patients (P23H, G106R) showed an inferior-superior retinal disease gradient of photoreceptor structural and functional abnormalities as well as retinal lamination changes. The superior retina could have normal thresholds but increased total retinal thickness; all retinal laminae were present. Rod threshold elevation was associated with photoreceptor segment signal abnormalities and ONL thinning. With increasing disease, there were major losses of outer retinal structure, but total retinal thickness could be maintained; this was attributable to thickened inner retina. Late stage disease showed thinned retina with a bilaminar-appearing inner retina. Class A patients (R135W, R135T, P347L) as young as age 6 showed thinned ONL and only cone-mediated vision. Blind retina had bilaminar-appearing residual inner retinal structure that was thick in most patients.

Conclusions:: In vivo evidence of retinal remodeling was found in both classes of RP caused by RHO mutations. Class B patients showed a range of abnormalities from normal retinal architecture and vision to remodeled, blind retina. Class A patients had relatively thick and remodeled retinas from the earliest ages studied. The results increase understanding of the sequence of retinal remodeling changes in human retinal degenerations and have implications for therapeutic strategies in this common form of RP.

Keywords: retinal degenerations: hereditary • imaging methods (CT, FA, ICG, MRI, OCT, RTA, SLO, ultrasound) • plasticity