Implication of Hyperhomocysteinemia in Blood Retinal Barrier (BRB) Dysfunction

Area of Science:

• Ophthalmology
• Neurology
• Cardiovascular Science

Background:

• Elevated plasma homocysteine (HHcy) is a risk factor for cardiovascular disease (CVD), diabetic retinopathy (DR), and age-related macular degeneration (AMD).
• HHcy is implicated in neurological diseases, including Alzheimer's disease (AD), through mechanisms like brain inflammation and blood-brain barrier (BBB) dysfunction.

Purpose of the Study:

• To review the effects of HHcy on the blood-retinal barrier (BRB).
• To discuss the role of HHcy in the pathogenesis of aging neurological diseases such as DR, AMD, and AD.
• To highlight potential mechanisms underlying HHcy-induced visual and neurological dysfunction.

Main Methods:

• Review of existing literature on hyperhomocysteinemia and its impact on ocular and neurological systems.
• Analysis of in vivo and in vitro studies investigating HHcy-induced BRB and BBB dysfunction.
• Exploration of proposed mechanisms including oxidative stress, ER stress, inflammation, epigenetic modifications, and N-methyl-D-aspartate receptor (NMDAR) activation.

Main Results:

• HHcy impairs both inner and outer BRB function, a key factor in vision loss in DR and AMD.
• HHcy induces brain inflammation, contributing to BBB dysfunction and AD pathogenesis.
• Oxidative stress, ER stress, inflammation, epigenetic changes, and NMDAR activation are implicated in HHcy-induced barrier dysfunction.

Conclusions:

• HHcy is a significant risk factor for BRB dysfunction and associated visual impairments.
• HHcy plays a controversial but potentially significant role in the pathogenesis of aging neurological diseases like AD.
• Understanding HHcy's mechanisms is crucial for developing therapeutic strategies for related visual and neurological disorders.