Novel techniques to prevent apoptosis and improve regeneration in corneal endothelial cells

ABSTRACT

Introduction

Human corneal endothelial cells (HCECs) play pivotal roles in maintaining corneal transparency, integrity, and thickness. However, their proliferation ceases in a mature human corneal endothelium. Thus, excessive loss of HCECs will result in decompensation of the corneal endothelium, which leads to corneal edema and visual loss eventually. Therefore, finding ways to inhibit apoptosis in HCECs is urgent for both clinical and basic research in ophthalmology.

Areas covered

The apoptotic mechanism of HCEC due to disease, eye drop, and ultraviolet A (UVA) with corresponding strategies and techniques to inhibit the apoptosis in the HCECs.

Expert opinion

The suitable treatment for Fuchs endothelial corneal dystrophy is to inject antioxidants directly or combined with anesthetic agent into anterior chamber during the ophthalmic surgery and administrate antibiotics and Stat3 activator post-operatively to prevent inflammation and apoptosis. Moreover, antioxidants, ROCK inhibitor, transgenic techniques, and apoptotic antagonists can be employed to interrupt the critical sections of intrinsic and extrinsic apoptotic pathways activated by eyedrop or UVA. These methods exhibit great promise in in vitro and animal studies, but so far none of these approaches has been shown to be safe and effective for prevention of apoptosis in human clinical trials.

KEYWORDS:

• Human corneal endothelial cell
• apoptosis
• anti-apoptosis
• intrinsic signal pathway
• extrinsic signal pathway

Article highlights

• UVA radiation, mechanical trauma, diseases, and drugs cause apoptosis of HCEC through receptor-mediated and/or mitochondrial-dependent pathway.

• Antioxidants efficiently prevent oxidative stressed HCECs from apoptosis.

• Transfecting anti-apoptotic protein can effectively improve the survival and viability of HCECs.

• ROCK inhibitors efficiently protect HCECs from apoptosis.

• Some ROCK inhibitors are applied in clinics in many countries and antioxidants in the stage of clinical trials are promising to be significant in clinics and economy.

• Neoplastic transformation of gene therapy should be concerned in clinic.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants, or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was supported by the National Key Research and Development Program of China [2017YFE0103500] from the Ministry of Science and Technology of the People’s Republic of China.