Dopamine Metabolites: Role in Age–Related and Post–Vitrectomy Cataracts

Abstract

Abstract: : Purpose: 1). To determine the levels of dopamine and biogenic amines in dense nucleus of Age Related Cataracts (ARC) and in aqueous humor (AH) and vitreous humor (VH) after vitrectomy with peeling of retinal membranes. 2). To determine the role of dopamine and derivatives on crystallines and lenses in culture. Methods: Nucleus from ARC and from autopsy eyes (New York Eye Bank) were digested with pronase in 0.1 M Tris Buffer ph 8.0, methanol/water extracted and phenol + fluorescent areas identified by TLC. In AH and VH of 4 patients post vitrectomy from retinal membranes; dopamine, other amines (DOPAC, HVA) and DOPAL (dehydroxyphenylacetaldelyde) was determine by GC–MS. Membranes of lens fibers and α, ß–M crystallines from humans and rabbit lenses were exposed to dopamine metabolites and tested for aggregation. Intact lenses were incubated in vitro in Dulbecco’s media with dopamine or methyldopamine and tested for Rb⁸⁶ transport and efflux, transparency and crystallin aggregations. Results: Dopamine, DOPAL, DOPAC and HVA levels in AH and VH increased significantly (255% to 760%) after retinal peeling indicating release of the amines from the retina. In ARC dopamine, HVA, DOPAC and DOPAL were identified in various fluorescent pigment of the dense cataract nucleus. Lenses incubated with 2mM methyldopamine for 5 days showed opacities, yellow–browning and changes in Rb⁸⁶ transport (↓28 ± 3%) and efflux (↑82 ± 5%). Similarly, aggregation of crystallines took place when incubated with dopamine + MOA, or DOPAL but not with DOPAC or HVA. Conclusions: The fluorescent pigments of ARC contain dopamine derivatives including DOPAL which could result in crystalline aggregation and opacification. A role of these aldehydes and biogenic amines is postulated for nuclear sclerosis of ARC and nuclear lens opacities after vitrectomy for retinal peeling.

Keywords: cataract • dopamine • vitreous