Year: 2026
Type: article
Abstract: Age-related macular degeneration (AMD) is classically defined by photoreceptor and retinal pigment epithelium degeneration; however, increasing evidence suggests that retinal ganglion cells (RGCs) may also be affected. The RGCs, including intrinsically photosensitive RGCs (ipRGCs), play essential roles in visual and non-image-forming functions, yet their vulnerability in the human dry AMD macula remains poorly understood. Here, we performed single-nucleus RNA sequencing (snRNA-seq) of macular tissue from non-AMD and dry AMD human donor eyes to comprehensively assess RGC populations and subtype-specific alterations. The clustering and re-embedding identified distribution of RGC subtypes across distinct transcriptional clusters, with no evidence of global RGC depletion in dry AMD. Comparative analyses revealed largely preserved expression of pan-RGC markers and subtype-specific genes across dry AMD maculae. Notably, ipRGCs, defined by expression of melanopsin (OPN4) and the transcription factor EOMES, exhibited stable spatial distribution, consistent cluster enrichment, and comparable transcriptional levels between non-AMD and dry AMD samples. Log₂ fold-change and volcano plot analyses further confirmed the absence of selective loss or transcriptional dysregulation of ipRGC markers in dry AMD. Together, these findings demonstrate that RGCs, including the melanopsin-rich ipRGC population, are transcriptionally preserved in the human dry AMD macula. This study provides critical insight into inner retinal neuronal resilience in dry AMD and establishes a foundation for future investigations into focusing ipRGC based neuroprotective strategies targeting RGCs in advanced stages of AMD.
Source: Scientific Reports
Authors: Shahna S. Hameed, Tasneem P. Sharma
Institution: Indiana University School of Medicine
Language: English
Subfield: Ophthalmology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,690
OpenAlex ID: W7155532200