Understanding Macula-Off Rhegmatogenous Retinal Detachment through Vitreous Proteomics

Abstract

Purpose : Rhegmatogenous retinal detachment (RRD) is a vision-threatening condition that results from a full-thickness retinal break with subsequent separation of the neurosensory retina from the apposing retinal pigment epithelium. Proteomic analysis of vitreous can identify proteins and pathways that play critical roles in retinal disease. This study examines vitreous proteome changes in RRD.

Methods : Vitreous fluid was collected from patients undergoing repair of epiretinal membrane (controls, n=10), acute RRD (n=11), and chronic RRD (n=10) for the Kellogg Eye Center Vitreous Biorepository. Acute RRD included detachments present for <7 days, whereas chronic RRD included those present for ≥7 days. All RRDs involved the fovea. Samples were processed according to protocols developed by our group and distributed across three 16-plexes for TMT-MS. Aliquoted pooled samples derived from a mix of equal parts acute RRD, chronic RRD, and ERM vitreous were used in each plex to enable inter-plex normalization. Ingenuity Pathway Analysis was used to infer biological meaning; z-scores demonstrating pathway activation were calculated with this software. This study was approved by the University of Michigan and Penn State College of Medicine institutional review boards and adhered to the tenets of the Declaration of Helsinki.

Results : The number of unique proteins was 1,560. Strong differential expression was observed between the RRD groups and controls. Between acute and chronic RRD, no proteins were different at a 10% false-discovery rate, so these samples were combined into a single RRD group. Pathway analysis demonstrated significantly increased activity in 24 pathways (z-scores in parentheses), including integrin signaling (4.47), actin signaling (3.53), and glucose metabolism (3.50). Four pathways demonstrated decreased activity, including LXR/RXR activation (-3.89) and DHCR24 signaling (-3.86).

Conclusions : These data demonstrate minimal effects of RRD duration on the vitreous proteome and a major change in the RRD proteome relative to controls. Activated pathways include those related to the RPE-photoreceptor interface and glucose metabolism. Deactivated pathways included retinoid modulation and a cholesterol metabolism pathway involved in lipid raft formation. A better understanding of the proteome changes in RRD may facilitate prognostic evaluation and development of new therapies.

This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.