Human recombinant Galectin-1 mitigates the cellular mechanisms of proliferative vitreoretinopathy in primary human tractive membranes in-vitro

Abstract

Purpose : Proliferative vitreoretinopathy (PVR) is the most common cause of a repeated complicated retinal detachment. Galectins are endogenous lectins which can influence a wide variety of cellular processes and are implicated in PVR pathogenesis. Via binding to glycans on cell membrane of myofibroblast-like retinal pigment epithelium (RPE) a modified cellular behavior has been demonstrated after exposure to exogenous Galectin-1 in vitro. The following is to determine the effect of Galectin-1 on primary cells derived from epiretinal membranes as a novel disease model and therapeutic target.

Methods : All procedures were approved by the institutional review board (IRB). Primary human PVR epiretinal membranes were obtained from four patients during pars plana vitrectomy and immediately attached to the cell culture plastic using small entomological pins. Incubation followed under standard cell culture conditions untill cells colonized the plastic around the membrane. Time-lapse microscopy was utilized to determinecell behavior. A longitudinal design was used. Cells were first imaged every 20 min for 16 h which was followed by the addition of 190 µg/ml human recombinant Galectin-1 and consecutive observation of the same cells for another 16 h. To determine the difference in cell behavior with and without Galectin cell migration tracks of 150 individual cells per patient were marked manually and the velocity as well as the degree of random and directed movement were analyzed. The number of mitotic events was quantified.

Results : Cell migration velocity was significantly reduced from 0.24 µm/min to 0.14 µm/min under Gal-1 exposure (p<.001 ). Galectin-1 furthermore reduced the fluidity in migrational behavior resulting in a less direct and more condensed migration pattern. Galectin 1 led to a significantly reduced number of mitotic events.

Conclusions : Exogenous recombinant Galectin-1 reduced the key mechanisms of PVR in cells from surgically removed primary epiretinal membranes. This could represent a possible new target in the prophylaxis and therapy of PVR.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.