Background and Objective: Limbal stem cell deficiency (LSCD) is characterized by the insufficiency of limbal stem cells to maintain the corneal epithelium. Severe cases of LSCD may be treated with limbal transplantation from healthy autologous or allogeneic limbal tissue. Multiple cell-based therapies have been studied as alternative treatments to improve success rates and minimize immunosuppressive regimens after allogeneic transplants. In this review, we describe the success rates, and complications of different cell-based therapies for LSCD. We also discuss each therapy’s relative strengths and weaknesses, their history in animal and human studies, and their effectiveness compared to traditional transplants.

Methods: PubMed was searched for publications using the terms LSCD, cell-based therapy, cultivated limbal epithelial transplantation (CLET), cultivated oral mucosal epithelial transplantation (COMET),and mesenchymal stem cells from 1989 to August 2022. Inclusion criteria were English language articles.Exclusion criteria were non-English language articles.

Key Content and Findings: current cell-based therapies for LSCD are CLET and non-limbal epithelial cells. Non-limbal epithelial cell methods include COMET, conjunctival epithelial autografts, and mesenchymal stem/stromal cells (MSCs). Moreover, several alternative potential sources of non-limbal cells have described, including induced pluripotent stem cells (iPSCs), human embryonic stem cells (hESCs),human dental pulp stem cells, hair follicle bulge-derived epithelial stem cells, amniotic membrane epithelial cells, and human umbilical cord lining epithelial cells.

Conclusions: Cell-based therapies are a promising treatment modality for LSCD. While CLET is currently the only approved cell-based therapy and is only approved in the European Union, more novel methods have also been shown to be effective in human or animal studies thus far. Non-limbal epithelial cells such as COMET are also an alternative treatment to allogeneic transplants especially as a surface stabilizing procedure. iPSCs are currently being studied in early phase trials and have the potential to revolutionize the way LSCD is treated. Lastly, cell-based therapies for restoring the limbal niche such as mesenchymal stem cells have also shown promising results in the first human proof-of-concept study. Several potential sources of non-limbal cells are under investigation.

Background: A variety of experimental animal models are used in basic ophthalmological research to elucidate physiological mechanisms of vision and disease pathogenesis. The choice of animal model is based on the measurability of specific parameters or structures, the applicability of clinical measurement technologies, and the similarity to human eye function. Studies of eye pathology usually compare optical parameters between a healthy and altered state, so accurate baseline assessments are critical, but few reports have comprehensively examined the normal anatomical structures and physiological functions in these models.

Methods: Three cynomolgus monkeys, six New Zealand rabbits, ten Sprague Dawley (SD) rats, and BALB/c mice were examined by fundus photography (FP), fundus fluorescein angiography (FFA), and optical coherence tomography (OCT).

Results: Most retinal structures of cynomolgus monkey were anatomically similar to the corresponding human structures as revealed by FP, FFA, and OCT. New Zealand rabbits have large eyeballs, but they have large optic disc and myelinated retinal nerve fibers in their retinas, and the growth pattern of retinal vessels were also different to the human retinas. Unlike monkeys and rabbits, the retinal vessels of SD rats and BALB/c mice were widely distributed and clear. The OCT performance of them were similar with human beings except the macular.

Conclusions: Monkey is a good model to study changes in retinal structure associated with fundus disease, rabbits are not suitable for studies on retinal vessel diseases and optic nerve diseases, and rats and mice are good models for retinal vascular diseases. These measures will help guide the choice of model and measurement technology and reduce the number of experimental animals required.

Background: Our national collaborative research initiative is proposing to develop a common infrastructure for Rb research. We are proposing a novel in vivo Rb model using human Rb cells line.

Methods: The rabbit model has advantages over the mouse models: (I) the larger eye size of rabbits, similar to the human infant eye, permits a more accurate injection of the drugs and evaluation of methods of targeted intraocular drug delivery; (II) the rabbit model demonstrated similar fundus appearance and pathologic features to human Rb, including vitreous seeds of viable tumor when the retinal tumor is mid-sized, which are usually found in the late stage in mouse models. The lack of ability to eliminate vitreous seeds is a major reason of current treatment failures in Group C and D tumors; therefore, the rabbit model of Rb may be used as a model to evaluate the effectiveness and various routes of drug delivery.

Results: This is an implementation of an infrastructure for evaluating therapeutic targets. In addition, this finding enables a variety of pharmacokinetic studies, pharmacodynamic and toxicology studies for new therapeutic agents.

Conclusions: This infrastructure meets the growing concern of practitioners and researchers in the field. The common facility is easily accessible to all VHRN members on request, including requests from other sectors.

Abstract: Corneal blindness represents one of the world’s three major causes of blindness, and the fundamental problem of corneal transplantation is a severe shortage of donor tissues worldwide, resulting in approximately 1.5 million new cases of blindness annually. To address the growing need for corneal transplants two main approaches are being pursued: allogenic and bioengineering cornea. Bioengineering corneas are constructed by naturally generating an extracellular matrix (ECM) component as the scaffold structure with or without corneal cells. It is well established that the scaffold structure directs the fate of cells, therefore, the fabrication of the correct scaffold structure components could produce an ideal corneal substitute, able to mimic the native corneal function. Another key factor in the construction of tissue engineering cornea is seed cells. However, unlike the epithelium and stroma cells, human cornea endothelium cells (HCECs) are notorious for having a limited proliferative capacity in vivo because of the mitotic block at the G1 phase of the cell cycle due to “contact-inhibition”. This review will focus on the main concepts of recent progress towards the scaffold and seed cells, especially endothelial cells for bioengineering cornea, along with future perspectives.

Abstract: Since the 21st century, the development of corneal tissue engineering technology has been developing rapidly. With the progress of biomaterials, cell culture and tissue engineering technology, tissue engineering cornea has gained great development in both basic scientific research and clinical application. In particular, tissue engineered corneal scaffolds are the core components of tissue engineered corneas. It is the focus of current research on tissue engineering cornea to search for scaffolds with good biocompatibility, high safety and good biomechanical properties. In this paper, the recent research progress of tissue engineering corneal materials is reviewed.

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.