Klotho: A new therapeutic target in diabetic retinopathy?

Table 1 Main effects of Klotho on retinal cells

Functions	Effects of Klotho depletion	Effects of treatment with Klotho	Type of cell	Ref.
Phagocytosis	Reduced	Improved	RPE cells	[41,43]
		Increased expression of Mertk
VEGF-A		Decreased secretion	RPE cells	[41]
		Reduced signaling mediated by VEGFR2- and IGF-1R
Redox balance	Increased oxidative stress	Restored	RPE cells	[41,53]
		Prevention of ROS production
		Increased NRF2 expression and nuclear translocation
	Reduced expression of SOD2	Restored expression of SOD2 and CAT
Pigmentation	Reduced		RPE cells	[41]
	Decreased melanin granules
Mitochondrial function	Reduced biogenesis of mitochondria	Preserved	RPE cells	[53]
Autophagy		Improved	Retina	[42]
	Decreased activation of AMPK
	Reduced expression of SIRT1
EMT		Decreased expression of mesenchymal cell markers	RPE cells	[66]
Apoptosis		Reduced	RPE and retinal endothelial cells	[42,53,54]
		Increased expression of Bcl-2
		Decreased expression of Bax
		Decreased activity of Caspase-3

VEGF-A: Vascular endothelial growth factor A; IGF-1R: Insulin-like growth factor-1; RPE: Retinal pigment epithelium; ROS: Reactive oxygen species; AMPK: 5' adenosine monophosphate-activated protein kinase; SIRT1: Silent information regulator 1; EMT: Epithelial-mesenchymal transition; NRF2: Nuclear factor E2-related factor 2; SOD2: Superoxide dismutase 2; CAT: Catalase.