Neuroprotective Agents for Photoreceptor Rescue Following Experimental Retinal Detachment in Rodents: A Systematic Review.

PURPOSE: The purpose of this study was to systematically evaluate neuroprotective interventions for photoreceptor preservation in rodent models of retinal detachment (RD).

METHODS

A systematic search of PubMed, Embase, Web of Science, and Google Scholar identified studies evaluating neuroprotective agents in rodent RD models. The primary outcome was a reduction in terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive cells quantified on retinal tissue sections (histology-based); secondary outcomes included preservation of the outer nuclear layer (ONL) and electroretinography (ERG). Risk of bias was assessed using the Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE) tool.

RESULTS

Thirty-six studies (2007-2025) met inclusion criteria: 19 rat, 12 mouse, and 5 combined-species. Interventions included small molecules and recombinant proteins (n = 30), monoclonal antibodies (n = 3), peptides (n = 2), and extracellular vesicle therapy (n = 1). Eight (22.2%) evaluated US Food and Drug Administration (FDA)-approved agents for non-retinal indications. Anti-inflammatory interventions achieved the highest median TUNEL reduction (84.5%, interquartile range [IQR] = 62.3%-88.1%), followed by anti-inflammatory/antioxidant approaches (70.8%, IQR = 54.3%-76.0%), metabolic modulators (59.6%, IQR = 42.9%-64.8%), and anti-apoptotic agents (59.0%, IQR = 56.6%-69.3%). Between-group differences were not statistically significant (Kruskal-Wallis P = 0.32). Quantitative ERG data were available in only six studies (16.7%). The risk of bias was largely unclear across selection and performance domains, with assessor blinding most reported (63.9% low risk). Ten studies additionally evaluated genetically modified backgrounds as complementary mechanistic strata (n = 11 experiments).

CONCLUSIONS

Inflammation-targeted therapies showed the most consistent numerical photoreceptor rescue across rodent RD studies. With eight studies evaluating FDA-approved agents, the field has clear repurposing opportunities; closing the translational gap will require rigorously designed, functionally oriented preclinical trials that reflect clinically realistic treatment delays.