Peptide Lv Deficiency Adversely Impacts the Structural and Functional Integrity of the Neural Retina.

Purpose: Peptide Lv (PLv) is a small endogenous secretory peptide expressed in various organs, including the retina and brain. It augments the protein expression and current densities of the L-type voltage-gated calcium channels in photoreceptors, hence the name peptide "Lv." However, its physiological function in the neural retina remains unknown. This study aims to determine the role of PLv in the retina using PLv null (PLv-/-) mice. Methods: Both male and female PLv-/- and age-matched control (PLv+/+) littermates were assessed longitudinally. The retinal light responses were examined using dark-adapted electroretinography (ERG). The thicknesses for whole retinas and various retinal layers were evaluated through spectral-domain optical coherence tomography (SD-OCT) and hematoxylin and eosin staining of retinal sections. Results: Dark-adapted ERG a-wave, b-wave, and oscillatory potentials were compromised in PLv-/- mice, which were more severe in females at younger ages. The whole retina and outer nuclear layer in PLv-/- mice were progressively thinner than the controls, as observed in SD-OCT imaging, which was corroborated by the histologic analyses of retinal sections. The progression of age-related retinal thinning was significantly slower in females than in males in both PLv-/- and PLv+/+ mice. Conclusions: Peptide Lv contributes to the maintenance of the structural and functional integrity of adult retinas, and its deficiency accelerates retinal degeneration. These findings highlight a potential neuroprotective role of peptide Lv in the retina.