Novel insights of minocycline as a neurovascular protective agent in retinitis pigmentosa.

Abstract

Retinitis pigmentosa (RP) is characterised by progressive photoreceptor degeneration accompanied by vascular abnormalities. We have previously demonstrated that minocycline exhibits therapeutic potential in RP. This trial aimed to evaluate its neurovascular protective effects. Patients with RP were enrolled and administered 100 mg of minocycline once daily for 12 months. A total of 32 eyes from 16 participants were included. The primary outcomes were changes in retinal and choroidal vasculature, including vessel density, lacunarity, foveal avascular zone (FAZ) area, fluorescein angiography (FA) score and subfoveal choroidal thickness (SFCT). The secondary outcomes included changes in photoreceptor structure and function, including ellipsoid zone width, best-corrected visual acuity (BCVA), mean macular sensitivity, mean deviation (MD) and error score. Adverse events were recorded. Additionally, Rd1 mice were used to further investigate the vascular effects of minocycline. After 12-month minocycline treatment, RP patients exhibited increased vessel density in both the retinal superficial capillary plexus (SCP) and retinal deep capillary plexus (DCP), accompanied by reduced FAZ area and decreased lacunarity in the SCP and DCP. FA score and SFCT remained stable, as did all secondary outcomes. A total of 24 adverse events were reported in 8 patients, and all resolved spontaneously without additional intervention. Additional experiments in Rd1 mice demonstrated improved retinal vascular abnormalities and preserved blood-retinal barrier integrity, accompanied by upregulated expression of tight junction proteins. Oral 100 mg minocycline once daily for 12 months was beneficial to protect vascular integrity and stabilise photoreceptor structure and function with good tolerability.