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. Author manuscript; available in PMC: 2023 Jul 1.
Published in final edited form as: Prog Retin Eye Res. 2022 Jan 4;89:101039. doi: 10.1016/j.preteyeres.2021.101039

Table 1.

Summary of neurotrophic factors in the diabetic cornea

Name Secretion Functions References
SP Nerves (1) Accelerate epithelial wound healing.
(2) Recovery of corneal sensation.
(3) Improve the mitochondrial function.
(4) Activate of Akt, EGFR, and Sirt1 through NK-1R.		 (Yang et al., 2014)
VIP Nerves (1) Stimulate corneal wound healing.
(2) Promote nerve regeneration.
(3) Regulate the wounding inflammatory response.
(4) Activate the Sonic Hedgehog signaling pathway.		 (Zhang et al., 2020a)
MANF CEC (1) Stimulate corneal wound healing.
(2) Promote nerve regeneration.
(3) Inhibit ER stress and apoptosis.
(4) Activate AKT signaling pathway.		 (Wang et al., 2020)
IGF-1 CEC (1) Promote the expression of stem cell markers.
(2) Increase corneal subbasal nerve density.		 (Ueno et al., 2014)
NGF Nerves, CEC (1) Promote neurite outgrowth and nerve regeneration.
(2) Stimulate corneal epithelial wound healing.		 (Di et al., 2017a)
GDNF Nerves and CEC (1) Promote neurite outgrowth and nerve regeneration.
(2) Induce corneal epithelial regeneration.		 (Di et al., 2017a)
PEDF Nerves and CEC (1) Increase nerve regeneration.
(2) Elevate corneal sensitivity and tear production.
(3) Accelerate corneal wound healing, selectively recruit type 2 macrophages, and prevent neutrophil infiltration.		 (He et al., 2017)
VEGF-B CEC (1) Promote nerve regeneration.
(2) Activate PI-3K/Akt-Gsk3ß-mTOR signaling pathway.
(3) Elevate the corneal content of PEDF.		 (Di et al., 2017b)
CNTF Nerves and Immune cells (1) Accelerate corneal wound healing.
(2) Promote nerve regeneration.
(3) Stimulate the mitosis of epithelial stem/progenitor cells.		 (Zhou et al., 2015)
EGF CEC (1) Stimulate corneal wound closure.
(2) Activate Akt signaling pathway.		 (Xu et al., 2009)
Netrin-1 Nerves (1) Promote corneal wound healing.
(2) Reactivate the phosphorylation of ERK and EGFR signaling.
(3) Decrease inflammation
(4) Promote M2 macrophage transition.		 (Zhang et al., 2018)
HGF CEC (1) HGF receptor c-met accelerates corneal wound healing.
(2) Reverse alterations the epithelial stem cell marker patterns		 (Saghizadeh et al., 2005)
Il-22 Immune cells (1) Promote epithelial cell regeneration
(2) Control tissue Inflammation through IL-10 expression		 (Gao and Xiang, 2019)

SP: substance P; VIP: Vasoactive intestinal peptide; MANF: Mesencephalic Astrocyte Derived Neurotrophic Factor; IGF-1: Insulin-like growth factor-1; NGF: Nerve growth factor; GDNF: Glial Cell Derived Neurotrophic Factor; PEDF: Pigment epithelium-derived factor; VEGF-BVascular endothelial growth factor B; CNTF: Ciliary Neurotrophic Factor; EGF: Epidermal Growth Factor; HGF: hepatocyte growth factor; IL-22: interleukin-22.