Diurnal Photoreceptor Outer Segment Renewal in Mice Is Independent of Galectin-3.

Galectin-3 (gal-3) is a soluble glycoprotein that has been associated with diverse forms of phagocytosis, including some mediated by the engulfment receptor MerTK. Retinal pigment epithelium (RPE) in vivo uses MerTK (or the related Tyro3) for phagocytosis of shed outer segment fragments during diurnal outer segment renewal. Here, we test if gal-3 plays a role in outer segment renewal in mice and if exogenous gal-3 can promote MerTK-dependent engulfment of isolated outer segment fragments by primary RPE cells in culture. We explored age- and strain-matched wild-type (wt), lgals3-/- and mertk-/- mice. Immunofluorescence and immunoblotting characterized gal-3 and RPE/retina protein expression, respectively. Outer segment renewal was investigated by live imaging of phosphatidylserine (PS) exposure on photoreceptor outer segment distal tips and by microscopy of rhodopsin-labeled RPE phagosomes in tissue sections. Retinal function was assessed by recording electroretinograms (ERGs). Phagocytosis assays feeding purified outer segment fragments (POS) were conducted with added recombinant proteins testing unpassaged primary mouse RPE. Gal-3 localizes to neural retina and RPE in wt mice. The lgals3-/- photoreceptor outer segments display normal diurnal PS exposure at distal tips. The number of rhodopsin-positive phagosomes in wt and lgals3-/- RPE does not differ at peak or trough of diurnal phagocytosis activity. lgals3-/- mice show light responses like wt, and their eyes contain wt levels of retinal and RPE proteins. Unlike purified protein S, recombinant gal-3 fails to promote POS engulfment by mouse primary RPE in culture. Gal-3 has no essential role in MerTK-dependent outer segment renewal in mice.

Citation

Nicholas J Esposito, Francesca Mazzoni, Jade A Vargas, Silvia C Finnemann. Diurnal Photoreceptor Outer Segment Renewal in Mice Is Independent of Galectin-3. Investigative ophthalmology & visual science. 2021 Feb 01;62(2):7

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PMID: 33538769

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