Impaired expression of thrombospondin-1 in eyes with age related macular degeneration

Abstract

Aims: This study investigated the expression and localisation of thrombospondin-1 (TSP-1), a known antiangiogenic extracellular matrix protein, in normal aged control human eyes and eyes with age related macular degeneration (AMD). Methods: Immunohistochemical analysis with mouse anti-human TSP-1 antibody and mouse anti-human CD 34 antibody, as a blood vessel marker, was performed on frozen sections from macular and peripheral blocks of aged control donor eyes (n = 12; mean age 78.8 years), and eyes with AMD (n = 12; mean age 83.9 years). Pigment in retinal pigment epithelium (RPE) and choroidal melanocytes was bleached. Three independent observers scored the immunohistochemical reaction product. Results: In the macular region, TSP-1 expression was observed intensely in Bruch's membrane and weakly in RPE basement membrane, choriocapillaris, and the wall of large choroidal blood vessels in the aged control eyes. In eyes with AMD, TSP-1 immunoreactivity was significantly lower in all structures except RPE basement membrane (p,0.01). There was significantly lower TSP-1 in the far periphery than the equator and submacular regions in all eyes. TSP-1 immunoreactivity was low in choroidal neovascularisation (CNV), but it was high and diffuse in adjacent scar tissue. Conclusion: These findings suggest that decreased TSP-1 in Bruch's membrane and choroidal vessels during AMD may permit the formation of CNV.A ngiogenic ocular diseases, especially age related macular degeneration (AMD), are a leading cause of blindness in the elderly population in western world.

Protective Roles of the Fractalkine/CX3CL1-CX3CR1 Interactions in Alkali-Induced Corneal Neovascularization through Enhanced Antiangiogenic Factor Expression

“…TSP-1 levels in Bruch's membrane and choroidal vessels was decreased in age-related macular degeneration (AMD) and a reduction in TSP-1 may permit the formation of choroidal neovascularization (56). Moreover, TSP-1 deficiency and, to a lesser extent, TSP-2 deficiency resulted in enhanced CNV induced by suture placement (48).…”

Thrombospondin-based antiangiogenic therapy

“…In addition, AMD patients express decreased levels of TSP-1 in Bruch's membrane and choriocapillaris, which may result in a permissive environment for choroidal neovascularization (CNV). 42 These observations reveal that TSP-1 plays a significant role in ocular homeostasis and function and has the potential to be used as a therapeutic agent to fulfill unmet clinical needs in neovascular ocular disease.…”

A review of drug options in age-related macular degeneration therapy and potential new agents

“…Used in conjunction with an anti-VEGF agent, a profound angiostatic effect may be achieved given that various pathways in the angiogenesis cascade are being targeted. Similarly, the various endogenous inhibitors of angiogenesis, such as PEDF [52], thrombospondin [74] and endostatin [51] are being investigated as potential therapeutic agents. Mouse models of laser-induced CNV have shown PEDF to be effective in reducing CNV size.…”