Cornea and Anterior segment

AB089. Impact of WNK1 inhibition on corneal wound healing using a model of human tissue-engineered cornea

:-
 

Background: Because of its superficial anatomical localization, the cornea is particularly vulnerable to abrasive forces and various traumas, which can lead to significant visual impairments. Upon injury of the corneal epithelium, there are important changes that occur in the composition of the underlying extracellular matrix (ECM). Those changes are perceived by the integrins that recognize the ECM components as their ligand and activate different intracellular signalling pathways, ultimately leading to reepithelialisation and reorganization of the injured epithelium, both of which are necessary in order to restore the visual properties of the cornea. The goal of this study was to analyse the impact of the pharmacological inhibition of specific signal transduction mediators of integrin-dependant signalling pathways on corneal wound healing using both monolayers of hCECs and tissue-engineered human corneas (hTECs) as in vitro models.

Methods: hTECs were produced by the self-assembly approach and wounded with a 8-mm diameter biopsy punch. Total RNA and proteins were isolated from the wounded and unwounded hTECs to conduct gene profiling analyses and protein kinase arrays. The wounded tissues were then incubated with the WNK1 inhibitor WNK463 and wound healing was monitored over a period of 6 days. Control corneas were incubated with the vehicle alone (DMSO). The impact of WNK1 inhibition on hCECs monolayers was determined using a scratch wound assay.

Results: Gene profiling analyses and protein kinases arrays revealed important alterations in the expression and activity of several mediators from the integrin-dependent signalling pathways in response to the ECM changes taking place during corneal wound healing. Among these, WNK1 is considerably activated through phosphorylation during corneal wound healing. The pharmacological inhibition of WNK1 by WNK463 significantly reduced the dynamic of corneal wound closure in our hTECs and hCECs monolayers compared to their respective negative controls.

Conclusions: These results allowed the identification of WNK1 kinase as an important player for a proper healing of the cornea. Also, these results allowed for a better understanding of the cellular and molecular mechanisms involved in corneal wound healing and they may lead to the identification of new therapeutic targets in the field of corneal wounds.

Review Article

Scleral remodelling in myopia and its manipulation: a review of recent advances in scleral strengthening and myopia control

:-
 

Abstract: The biological mechanisms of eye growth and refractive development are increasingly well characterised, a result of many careful studies that have been carried out over many years. As the outer coat of the eye, the sclera has the ultimate impact on the restraint or facilitation of eye growth, thus any changes in its biochemistry, ultrastructure, gross morphology and/or biomechanical properties are critical in refractive error development and, in particular, the development of myopia. The current review briefly revisits our basic understanding of the structure and biomechanics of the sclera and how these are regulated and modified during eye growth and myopia development. The review then applies this knowledge in considering recent advances in our understanding of how the mechanisms of scleral remodelling may be manipulated or controlled, in order to constrain eye growth and limit the development of myopia, in particular the higher degrees of myopia that lead to vision loss and blindness. In doing so, the review specifically considers recent approaches to the strengthening of the sclera, through collagen cross-linking, scleral transplantation, implantation or injection of biomaterials, or the direct therapeutic targeting and manipulation of the biochemical mechanisms known to be involved in myopia development. These latest approaches to the control of scleral changes in myopia are, where possible, placed in the context of our understanding of scleral biology, in order to bring a more complete understanding of current and future therapeutic interventions in myopia, and their consequences.

Review Article

Narrative review of risuteganib for the treatment of dry age-related macular degeneration (AMD)

:-
 

Abstract: Age-related macular degeneration (AMD) is a leading cause of blindness worldwide. AMD most commonly affects older individuals and is characterized by irreversible degeneration of the retinal pigment epithelium and neurosensory retina. Currently, there are limited treatment options for dry AMD outside of lifestyle modification and nutrient supplementation. Risuteganib [Luminate (ALG-1001), Allegro Ophthalmics, CA, USA] is an intravitreally administered inhibitor of integrin heterodimers αVβ3, αVβ5, α5β1, and αMβ2. It is currently undergoing clinical trials for the treatment of dry AMD and diabetic macular edema (DME). Preclinical studies have shown that risuteganib has an effect on the pathways for angiogenesis, inflammation, and vascular permeability. Ongoing clinical trials have had promising results showing improvements in patient best corrected visual acuity (BCVA) and reduced central macular thickness measured by optical coherence tomography (OCT). There is a pressing need for treatments for dry AMD and while risuteganib appears to have a potential benefit for patients, more data are needed before one can truly evaluate its efficacy. This narrative review provides a concise summary of the most up to date data regarding the proposed mechanism of action of risuteganib in the treatment of nonexudative AMD and DME as well as the results from recent phase 1 and phase 2 clinical trials.

其他期刊
  • 眼科学报

    主管:中华人民共和国教育部
    主办: 中山大学
    承办: 中山大学中山眼科中心
    主编: 林浩添
    主管:中华人民共和国教育部
    主办: 中山大学
    浏览
  • Eye Science

    主管:中华人民共和国教育部
    主办: 中山大学
    承办: 中山大学中山眼科中心
    主编: 林浩添
    主管:中华人民共和国教育部
    主办: 中山大学
    浏览
出版者信息
中山大学中山眼科中心 版权所有粤ICP备:11021180