Photoreceptor survival mediated by PEDF is associated with Cone-Rod Homeobox (CRX) upregulation

Authors

• S Dixit
• SP Becerra

Abstract

PEDF delays photoreceptor death in retinal degeneration models. The absence of PEDF encoding gene Serpinf1, increases retinal cell death susceptibility in rd10 model of inherited retinal degeneration. While CRX is vital for photoreceptor differentiation and development, its role in photoreceptor survival is unclear. This study aims to investigate the effects of PEDF on changes in CRX in mouse retina using Serpinf1-/-, Serpinf1+/+, rd10, and rd10/Serpinf1-/- mice. Retinal explants were cultured and treated with PEDF, PEDF-H105A protein, and PEDF-derived peptides H105A and R99A. Zaprinast was used to induce photoreceptor cell death. H105A peptide eye drops were administered in vivo. qRT-PCR and immunofluorescence were used to analyze CRX at transcript and protein levels, respectively. The cellular distribution of CRX protein was altered in the photoreceptors of Serpinf1-/- mice compared to Serpinf1+/+ mice. CRX immunolabelling in photoreceptors of retinal explants from Serpinf1-/- mice was decreased. Exogenous PEDF treatment promoted survival and increased CRX detection in the photoreceptors of both Serpinf1+/+ and Serpinf1-/- retinal explants. Zaprinast induced photoreceptor cell death and reduced CRX, but PEDF treatment restored CRX levels in both Serpinf1+/+ and Serpinf1-/- retinal explants. PEDF-H105A and H105A peptide increased CRX in Serpinf1+/+ retinal explants, however R99A peptide had no effect. Crx transcripts of rd10 and rd10/Serpinf1-/- mice retinas were lower than Serpinf1+/+. H105A peptide eye drops transiently increased Crx gene expression in rd10 and rd10/Serpinf1-/- retinas. This study reveals a pivotal link between the PEDF neurotrophic activity and CRX upregulation via PEDF-R, highlighting the role of the CRX in photoreceptor survival.

Scientific Focus Area: Molecular Biology and Biochemistry

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