Ablation of Ctrp9, Ligand of AdipoR1, and Lower Number of Cone Photoreceptors in Mouse Retina

Abstract

Purpose C1q/TNF-related protein (CTRP) 9 is one of the adiponectin paralogs, and a genetic ablation of its receptor, AdipoR1, is known to cause retinal degeneration. The purpose of this study was to determine the role played by CTRP9 in the retina. Methods The retinas of Ctrp9 gene knockout (KO) and wild type (WT) mice were examined by electroretinography (ERG), histology, RNA sequencing, and quantitative real-time PCR. Results The amplitude of the photopic ERG elicited by the maximum stimulus intensity was smaller by 40% in the Ctrp9 KO mice than in WT mice at 8 weeks of age. However, the photopic ERGs was not reduced from 8 weeks to 6 months of age. The amplitudes of the scotopic ERGs were not reduced in the Ctrp9 KO mice at 8 weeks and 6 months of age. No distinct histological abnormalities were found in the retinal sections but the density of peanut agglutinin-stained cells in the retinal flat mount of KO mice was reduced to about 70% of that of WT mice. Genomewide RNA sequencing of the retina revealed the absence of the expression of CTRP9 in both KO and WT mice. RNA sequencing and quantitative real-time PCR analysis showed that the expressions of the transcripts of genes expressed in cones, Opn1sw , Opn1mw , Gnat2 , and Cnga3 , were reduced in the KO mice retina, however, the degree of expression of the transcripts in rods was not significantly reduced. Conclusions CTRP9 is released ectopically from other tissues, and it regulates the number of cones in the mouse retinas.

CTRP 9 mitigates the apoptosis and unfolded protein response of OGD/R-induced retinal ganglion cells by regulating the AMPK pathway

“…C1q/TNF-related protein-9 (CTRP9) is a newly discovered adipose tissue-derived cytokine, which is involved in the clearance of apoptotic cells by phagocytes, regulation of the inflammatory response and immune tolerance [8]. A previous study revealed that CTRP9 is associated with regulation of the biological roles of the retina [9]. CTRP9 is reported to attenuate retinal inflammation, protect the blood-retinal barrier, and alleviate the vascular leakage in the early stage of diabetic retinas [10].…”