Prophylactic fingolimod administration prevents the development of proliferative vitreoretinopathy in an experimental...

This study aimed to evaluate the prophylactic potential of fingolimod, an FDA-approved sphingosine-1-phosphate receptor modulator, in preventing proliferative vitreoretinopathy (PVR) in an experimental rat model induced by intravitreal platelet-rich plasma (PRP) injection.

Thirty-two male Wistar albino rats were randomly assigned to four groups (n = 8 per group): Control, Fingolimod, PVR, and PVR + Fingolimod. PVR was induced by intravitreal injection of autologous PRP in the PVR and PVR + Fingolimod groups. Fingolimod (0.3 mg/kg/day) was administered by oral gavage for 21 days to the rats in the Fingolimod and PVR + Fingolimod groups. Histopathological evaluation included grading of retinal folds, epiretinal membrane (ERM) scoring, staging of retinal detachment and assessments of overall PVR severity, vessel count, retinal thickness, vitreoretinal traction membrane presence, and retinal-layer disruption. Body weight was monitored at baseline and at euthanasia. A complete blood count was also performed.

Prophylactic fingolimod administration significantly reduced the indicators of PVR severity. The PVR + Fingolimod group showed significantly lower retinal fold grades (1.12 ± 0.99 vs. 3.25 ± 1.04, p < 0.001), ERM grades (1.25 ± 0.46 vs. 3.12 ± 0.99, p < 0.001), and retinal detachment grades (1.38 ± 0.52 vs. 2.75 ± 0.71, p < 0.001) than the PVR group. Neovascularization was significantly lower in the PVR + Fingolimod group (6.50 ± 1.31 vs. 10.50 ± 3.96 vessels, p < 0.001). Vitreoretinal traction membrane was present in 75% of eyes showing PVR but completely absent in the PVR + Fingolimod group (p < 0.05). Prophylactic fingolimod administration also significantly reduced white blood cell (3.75 ± 1.52 vs. 8.70 ± 2.39 × 10³/μL, p < 0.001) and lymphocyte (1.90 ± 0.90 vs. 6.86 ± 1.91 × 10³/μL, p < 0.001) counts. Post-hoc power analysis indicated statistical power > 0.80 for most primary endpoints. Body weight monitoring showed no overt systemic toxicity or weight loss.

To the best of our knowledge, this proof-of-concept study provides the first preclinical evidence that prophylactic fingolimod administration effectively prevents PVR development, consistent with anti-inflammatory and immunomodulatory mechanisms. Thus, Fingolimod represents a promising prophylactic candidate for PVR prevention, warranting further clinical investigation.