Inflammation-targeted therapies show highest photoreceptor rescue in rodent retinal detachment models, systematic review finds

Retinal detachment (RD) is a severe ophthalmic condition leading to rapid photoreceptor degeneration and irreversible vision loss. Current surgical interventions reattach the retina but often fail to prevent subsequent photoreceptor death, highlighting a critical need for neuroprotective strategies. Photoreceptor apoptosis, driven by inflammation, oxidative stress, and metabolic dysfunction, is a key mechanism of vision loss post-RD. Understanding which neuroprotective agents effectively preserve photoreceptors in preclinical models is crucial for developing new therapeutic approaches.

Researchers conducted a systematic review of PubMed, Embase, Web of Science, and Google Scholar to identify studies evaluating neuroprotective agents in rodent models of retinal detachment. Thirty-six studies (19 rat, 12 mouse, 5 combined-species) published between 2007 and 2025 met inclusion criteria. The primary outcome was reduction in TUNEL-positive cells (histology-based); secondary outcomes included outer nuclear layer (ONL) preservation and electroretinography (ERG). Risk of bias was assessed using the SYRCLE tool.

Thirty-six studies were included, evaluating various neuroprotective agents including small molecules, recombinant proteins (n = 30), monoclonal antibodies (n = 3), peptides (n = 2), and extracellular vesicle therapy (n = 1). Eight studies (22.2%) investigated FDA-approved agents for non-retinal indications. Interventions were categorized by mechanism: anti-inflammatory, anti-inflammatory/antioxidant, metabolic modulators, and anti-apoptotic agents.

Anti-inflammatory interventions achieved the highest median TUNEL reduction (84.5%, interquartile range [IQR] = 62.3%-88.1%), demonstrating superior photoreceptor rescue. This was 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%). However, between-group differences in TUNEL reduction were not statistically significant (Kruskal-Wallis P = 0.32). Quantitative ERG data, crucial for functional assessment, were available in only six studies (16.7%). Risk of bias was largely unclear, though assessor blinding was reported as low risk in 63.9% of studies.