Therapeutic potential of prolactin-releasing anti-dopaminergic agents in experimental diabetic retinopathy model

Abstract Purpose To investigate the ocular effects of prolactin elevation induced by anti-dopaminergic agents used for diabetic gastroparesis, including metoclopramide (MCP), trimethobenzamide (TMB), and domperidone (DOM), on intraocular pressure (IOP), tear production, and retinal angiogenesis-related markers in a streptozotocin-induced diabetic rat model. Methods Fifty Wistar rats were randomly divided into five groups ( n = 10 each): control, diabetes mellitus (DM), and DM treated with MCP, TMB, and DOM. Six weeks after diabetes induction, treatments were administered twice daily for two weeks. IOP and tear production (Schirmer test) were measured before enucleation. Retinal tissues were immunohistochemically analyzed for expression of the prolactin receptor, vascular endothelial growth factor (VEGF), and CD31. Staining intensity and the percentage of positive cells were semi-quantitatively scored, and mean values were compared among groups. Results IOP and tear production showed no significant intergroup differences. Retinal staining was most prominent in the ganglion cell layer; therefore, this region was analyzed in detail. Prolactin receptor expression was significantly increased in all treatment groups compared with the diabetic and control groups ( p < 0.05). VEGF and CD31 scores were elevated in the diabetic group but decreased with MCP, TMB, and DOM ( p < 0.05). Conclusions Prolactin-elevating antidopaminergic agents (MCP, TMB, and DOM) were associated with reduced immunoreactivity for VEGF and CD31 and increased expression of the prolactin receptor in the diabetic retina, without adverse effects on IOP or tear production. These findings warrant further investigation, including functional vascular assessments, to clarify their potential relevance in diabetic retinopathy.