The Expressions of Klotho Family Genes in Human Ocular Tissues and in Anterior Lens Capsules of Age-Related Cataract

Abstract

Purpose: Klotho genes are expressed in limited tissues and have been found to be a pathogenic factor of age-related diseases in mammals, but their expressions and functions in human eyes are yet to be defined. This study was performed to investigate the expression of Klotho family genes in human ocular tissues and anterior lens capsules of age-related cataract.

Methods: Individual tissues were isolated from human eyeballs collected from Henan Eye Bank. Human anterior lens capsules were collected from cortical cataract patients during phacoemulsification with the informed consent. Real-time quantitative reverse transcription was performed to detect the mRNA expressions of α-Klotho, β-Klotho, γ-Klotho, IGFR1, AKT, and ERK; Western blot analysis for detecting the expression of ERK1/2 and phosphor-ERK1/2 protein; and Pearson correlation analysis was performed to detect the relationship between Klotho genes and IGFR1, AKT or ERK genes.

Results: The expressions of α-, β-, and γ-Klotho mRNA were detected in human retina and optic nerve, but were not detected in iris, ciliary body, sclera, and choroid. Only α-and γ-Klotho mRNA expressions were detected in the lens, and the expression levels were higher than that in the retina and optic nerve. The mRNA expressions of IGFR1 and AKT were not changed among the transparent and the opaque lens capsules. The mRNA expression of ERK was significantly decreased in the opaque lens capsule. Correlation analysis showed that the ERK mRNA expression was positively correlated with the expression of the γ-Klotho gene. Western blot results showed a significant decrease of ERK1/2 and phosphor-ERK1/2 protein in opaque lens capsules.

Conclusions: α- and γ-Klotho genes express in the human retina, optic nerve, and lens. The β-Klotho gene expresses only in retina and optic nerve. The γ-Klotho gene may regulate human lens epithelial cells' function mainly by the MAPK/ERK1/2 signaling pathway.

Keywords: Age related; ERK; Klotho gene; cataract; ocular tissue; pathway.