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: Cornea serves as the partial front barrier and major light reflection organ of the eye. The integrity of corneal surface is essential for ocular function. Injuries or congenital diseases could significantly destruct the homeostasis of the ocular surface, especially the microenvironment of limbal epithelial stem cells (LESCs), and will eventually cause dysfunction of corneal regeneration and diminish of LESCs. The loss of LESCs by different reasons are named limbal stem cell deficiency (LSCD), which is one of the leading cause of vision loss worldwide. To restore the corneal surface, LESC transplantation in the form of tissue or cell cultures is currently a viable and promising method to treat LSCD. In this review, we aim to introduce the characters and niche of LESCs, and discuss different aspects of its application in cornea surface reconstruction.
Background: To investigate the effect of sirolimus (SRL) eye drops on acute alkali-burn-induced corneal neovascularization (CNV) and explore its possible mechanism.
Methods: A total of 57 male Sprague-Dawley rats weighing 160–180 g were randomly divided into four groups including a normal control group (NC group, n=12), an untreated alkali-burned model control group (MC group, n=15), a blank eye drop treatment group (BT group, n=15), and an SRL eye drop treatment group (ST group, n=15). Corneal inflammation and CNV were observed and scored under a slit-lamp microscope 3, 7, and 14 days after alkali exposure. Three rats were randomly sacrificed in each group before modeling and 3, 7, 14 days after modeling, and the corneas of right eyes were harvested for Western blotting to compare the expression levels of VEGFR2 and caspase-3.
Results: Corneal inflammation scoring showed that the corneal edema and conjunctival congestion were severe in the MC, BT, and ST groups 1 day after alkali exposure but were alleviated at day 3. The corneal transparency was significantly higher in the ST group than in the MC and BT groups at days 7 (F=9.77, P<0.05) and 14 (F=5.81, P<0.05). At day 1, the corneal limbal vascular network was markedly filled. SNV was obvious at days 3, 7, and 14. The new blood vessels were shorter and sparser in the ST group than in the MC and BT groups, and the CNV scores showed significant differences among these groups (day 3: F=8.60, P<0.05; day 7: F=11.40, P<0.05; and day 14: F=41.59, P<0.01). Western blotting showed that the expressions of VEGFR2 and caspase-3 were low before modeling and showed no significant difference among the different groups (F=0.52, P>0.05; F=0.98, P>0.05). The corneal expression of VEGFR2 became significantly higher in the MC and BT groups than in the ST group 3, 7, and 14 days after alkali exposure, and there were significant differences in relative gray-scale values among these groups (day 3: F=32.16, P<0.01; day 7: F=85.96, P<0.01; day 14: F=57.68, P<0.01). The increase in the corneal expression of caspase-3 was significantly larger in the ST group than in the MC and BT groups at days 3, 7, and 14, and there were significant differences in relative gray-scale values among groups (day 3: F=32.16, P<0.01; day 7: F=53.02, P<0.01; day 14: F=38.67, P<0.01).
Conclusions: SRL eye drops can alleviate acute alkali-burn-induced corneal inflammation and inhibit alkali-burn-induced CNV in rat models. It can reduce VEGFR2 expression and increase caspase-3 expression in the corneal tissue, which may contribute to the inhibition of alkali-burn-induced CNV.
Abstract: Acute retinal necrosis (ARN) is a devastating syndrome characterized by panuveitis, retinal necrosis, and a high rate of retinal detachment that may result in poor visual outcomes if not promptly diagnosed and treated. ARN is most commonly caused by viruses within the herpesvirus family. Etiologies include varicella-zoster virus, herpes simplex virus, and cytomegalovirus, and may be promptly diagnosed by polymerase chain reaction testing of aqueous or vitreous fluid. The true incidence of ARN is not known due to its rarity; as a result, clinical treatment is often guided by retrospective case series, case reports, and expert opinion. Standard of care has evolved over time but currently includes a combination of systemic and intravitreal antiviral in conjunction with topical or oral steroids and surgical therapy as needed. Combination therapy may reduce the rate of severe vision loss and increase the rate of visual acuity gain, although further studies are needed in this area. In particular for patients with mild to moderate disease, combination therapy may reduce the rate of retinal detachment. Adjunctive therapies including oral corticosteroid and prophylactic laser barricade are incompletely studied, but corticosteroid in particular, may reduce inflammation, which also is involved in the severe disease pathogenesis observed in ARN. This review discusses the advances in diagnosis and treatment of ARN, including management with combination antiviral medication and surgical interventions.
Abstract: An intestinal dysbiosis is connected to a number of inflammatory diseases through various mechanisms relating to its effect on immune cell function and differentiation. This is a review of the literature summarizing our current understanding of intestinal microbial contributions to non-infectious uveitis and strategies to target the intestinal microbiome to treat uveitis. Several groups have demonstrated an intestinal dysbiosis associated with certain types of non-infectious uveitis. Additionally, approaches to treat uveitis by modifying the intestinal microbiota, such as oral antibiotics or administration of oral short chain fatty acids (SCFAs), which are intestinal bacterial metabolites produced by fermentation of dietary fiber, can successfully treat uveitis in mouse models. This reduction in severity of ocular inflammation occurs via the following mechanisms: enhancement of regulatory T cells, decreasing intestinal permeability, and/or affecting T cell trafficking between the intestines and the spleen. Other strategies that are directed at the intestinal microbiota that might be effective to treat uveitis include dietary changes, probiotics, or fecal microbial transplantation. The commensal gut bacteria are influential in systemic and intestinal mucosal immunity and thus contribute to the development of extraintestinal inflammation like uveitis. Targeting the intestinal microbiome thus has the potential to be a successful strategy to treat non-infectious uveitis.
Abstract: Uveitis can cause significant visual morbidity and often affects younger adults of working age. Anterior uveitis, or inflammation limited to the anterior chamber (AC), iris, and/or ciliary body comprises the majority of uveitis cases. Current clinical biomarkers and conventional grading scales for intraocular inflammation are mostly subjective and have only a moderate degree of interobserver reliability, and as such they have significant limitations when used in either clinical practice or research related to uveitis. In recent years, novel imaging techniques and applications have emerged that can supplement exam findings to detect subclinical disease, monitor quantitative biomarkers of disease progression or treatment effect, and provide overall a more nuanced understanding of disease entities. The first part of this review discusses automated algorithms for optical coherence tomography (OCT) image processing and analysis as a means to assess and describe intraocular inflammation with higher resolution than that afforded by conventional AC and vitreous cell ordinal grading scales. The second half of the review focuses on anterior segment OCT and OCT angiography (OCTA) in scleritis and iritis, especially with regards to their ability to directly image and characterize the pathologic structures and vasculature underlying these diseases. Finally, we briefly review experimental animal research with promising but more distant human clinical applications, including in vivo molecular microscopy of inflammatory markers and investigation of gold nanoparticles as a potential contrast agent in OCT imaging. Imaging modalities are discussed in the broader context of trends within the field of uveitis towards greater objectivity and quantifiable outcome measures and biomarkers.
Abstract: Effective and safe electrical stimulation of the retinal ganglion cells is at the heart of retinal prosthesis design. However, the effectiveness and safety demand of the electrical stimulation is often at odds against each other. Besides, the nerve fiber layer above retinal ganglion cells limits the spatial resolution of stimulation. Also, current retinal prosthesis still cannot selectively activate the ON or OFF visual pathways, thus cannot relay the correct luminance information to the brain. With decades of development, the stimulation protocol for retinal implants began to tackle these problems. We believe that a novel design of electrical stimulation scheme, combined with gene therapy technique, can improve the selectivity and spatial resolution of retinal implants and further lower the damage caused by electric stimulation.
