Idelalisib inhibits experimental proliferative vitroretinopathy

Area of Science:

• Ophthalmology
• Cell Biology
• Pharmacology

Background:

• Proliferative vitreoretinopathy (PVR) is a severe fibrotic complication following retinal detachment surgery or trauma.
• Retinal pigment epithelial (RPE) cells are key contributors to PVR pathogenesis.
• Phosphoinositide 3-kinase delta (PI3Kδ) is expressed in RPE cells and implicated in fibrotic processes.

Purpose of the Study:

• To investigate the potential of idelalisib, a PI3Kδ inhibitor, in preventing proliferative vitreoretinopathy (PVR).
• To evaluate the effects of idelalisib on fibrotic markers and cellular functions in RPE cells.
• To assess the efficacy of idelalisib in an experimental rabbit model of PVR.

Main Methods:

• GeoMx Digital Spatial Profiling to analyze fibronectin expression in epiretinal membranes.
• In vitro studies using human RPE cells treated with idelalisib and transforming growth factor-beta 2 (TGF-β2).
• In vivo studies involving experimental PVR induction in rabbits and treatment with intravitreal idelalisib, assessed via indirect ophthalmoscopy, electroretinography, optical coherence tomography, and histology.

Main Results:

• Idelalisib significantly inhibited Akt activation, fibronectin expression, and collagen gel contraction in TGF-β2-stimulated human RPE cells.
• Idelalisib at a non-toxic vitreal concentration (10 μM) effectively prevented experimental PVR in rabbits.
• Histological and functional assessments confirmed the PVR-preventive effects of idelalisib in the rabbit model.

Conclusions:

• Idelalisib demonstrates potent anti-fibrotic effects in RPE cells relevant to PVR.
• Idelalisib effectively prevents experimental PVR in a preclinical model.
• These findings support the potential therapeutic application of idelalisib for PVR prevention in humans.