Differential Survival of Retinal Ganglion Cell Types Following Branch Retinal Vein Occlusion

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Abstract
Purpose: Branch retinal vein occlusion (BRVO) is a common cause of retinal ischemia, rapidly inducing neuronal death and often producing irreversible vison loss. Interventions such as thrombolysis restore perfusion but cannot recover neurons already lost, and most patients retain permanent visual deficits. Identifying which neuronal populations die, and how rapidly, may therefore reveal timing windows and targets for neuroprotective treatment. To determine the timing of pathology, we evaluated vascular changes and neuronal degeneration in a photocoagulation-induced mouse model of BRVO. To determine differences in retinal ganglion cells (RGC) type susceptibility, we tracked the survival of RGC subpopulations using immunofluorescence markers. Methods: BRVO was induced by Rose Bengal injection followed by targeted photocoagulation of a branch vein. Obstruction was confirmed by fluorescein angiography and vascular damage assessed by optical coherence tomography angiography. Cell survival was quantified by immunostaining at 3, 7, and 14 days using RNA-Binding Protein with Multiple Splicing (RBPMS, pan-RGC). RGC subtype markers for intrinsically photosensitive RGCs (TBR2), α-RGCs (SPP1), ON–OFF direction-selective RGCs (CART), and F-RGCs (FOXP2) were used to compare subtype survival. Results: Occlusion selectively disrupted the superficial and intermediate capillary plexus, sparing the deep plexuses. All examined neuronal populations were significantly depleted, but with markedly different magnitude and timing. α-RGCs and F-RGCs were the most vulnerable subtypes, both approaching complete loss by one week, whereas intrinsically photosensitive RGCs were the most resistant. Conclusions: α-RGCs, typically resilient in glaucoma, trauma, and excitotoxicity, were markedly vulnerable in BRVO, indicating that RGC subtype susceptibility is insult-specific.
Funding Information
  • Research to Prevent Blindness
  • NIH grants (EY032908)
  • NIH grants (EY032908)
  • NIH grants (EY036111)
  • Richard and Isabel Goldstein Family Foundation
  • Jeffrey T. Fort Innovation Fund
  • Siteman Retina Research Fund
  • NIH P30 Core Grant

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