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The choroid is the richly vascular layer of the eye located between the sclera and Bruch's membrane. Early studies in animals, as well as more recent studies in humans, have demonstrated that the choroid is a dynamic, multifunctional structure, with its thickness directly and indirectly subject to modulation by a variety of physiologic and visual stimuli. In this review, the anatomy and function of the choroid are summarized and links between the choroid, eye growth regulation, and myopia, as demonstrated in animal models, discussed. Methods for quantifying choroidal thickness in the human eye and associated challenges are described, the literature examining choroidal changes in response to various visual stimuli and refractive error-related differences are summarized, and the potential implications of the latter for myopia are considered. This review also allowed for the reexamination of the hypothesis that short-term changes in choroidal thickness induced by pharmacologic, optical, or environmental stimuli are predictive of future long-term changes in axial elongation, and the speculation that short-term choroidal thickening can be used as a biomarker of treatment efficacy for myopia control therapies, with the general conclusion that current evidence is not sufficient.

Corneal curvature, a highly heritable trait, is a key clinical endophenotype for myopia - a major cause of visual impairment and blindness in the world. Here we present a trans-ethnic meta-analysis of corneal curvature GWAS in 44,042 individuals of Caucasian and Asian with replication in 88,218 UK Biobank data. We identified 47 loci (of which 26 are novel), with population-specific signals as well as shared signals across ethnicities. Some identified variants showed precise scaling in corneal curvature and eye elongation (i.e. axial length) to maintain eyes in emmetropia (i.e. HDAC11/FBLN2 rs2630445, RBP3 rs11204213); others exhibited association with myopia with little pleiotropic effects on eye elongation. Implicated genes are involved in extracellular matrix organization, developmental process for body and eye, connective tissue cartilage and glycosylation protein activities. Our study provides insights into population-specific novel genes for corneal curvature, and their pleiotropic effect in regulating eye size or conferring susceptibility to myopia.

Purpose The development of myopia in guinea pigs can be inhibited by attenuating scleral hypoxia by increasing choroidal blood perfusion (ChBP). In this study, we reduced ChBP through surgical and pharmacological methods to determine the effect on myopia development. We also determined whether ChBP was reduced by quinpirole, a drug that enhances form-deprivation myopia (FDM). Methods ChBP was reduced in the right eyes of guinea pigs via transection of the temporal ciliary arteries or daily injections of phenylephrine into the inferior peribulbar space for one week during normal ocular growth. Other guinea pigs were subjected to two weeks of monocular FDM—with facemasks, along with daily injections of quinpirole, a dopamine D2 receptor agonist, to enhance the FDM. Changes in refraction, axial length, ChBP, and choroidal thickness (ChT) were measured in both treated and fellow eyes of the treatment and control groups. Scleral hypoxia labeling with pimonidazole adducts and α-smooth muscle actin (α-SMA) protein were also measured. Results Surgical and pharmacological reduction of ChBP induced myopia development in the treated eyes. These treatments rendered the scleral hypoxia and increased scleral α-SMA expression. Furthermore, quinpirole injections, which increased the magnitude of myopia, augmented the FDM-associated reductions in ChBP and ChT and increased the levels of scleral hypoxia and α-SMA protein. Conclusions Decreased ChBP in guinea pigs leads to scleral hypoxia and scleral myofibroblast transdifferentiation with increased α-SMA expression, ultimately resulting in myopia development. In future clinical trials, ChBP reduction can serve as a potential biomarker for early detection of myopia development.

To study the feasibility of using basement membrane of human amniotic membrane (BMHAM) as a carrier for transplantation of cultivated cat corneal endothelial cells (cCCECs).BHMAM was obtained by enzymic digestion. cCCECs were seeded on the BMHAM and cultivated traditionally. The resulting continuous monolayer of cCCECs was transplanted onto the cat corneal graft stripped of the Descemet membrane with endothelium. To determine whether the transplanted cCCECs were vital and functional in vivo, the corneal grafts were examined by slit-lamp microscope every day for 6 weeks, and corneal thickness was measured by ultrasonic pachymetry. Either in vivo or in vitro, the cCCEC sheets on BMHAMs were examined morphologically by light and electron microscope, and the cell density was measured.Seven to 10 days after seeding on the BMHAM, the cCCECs were confluent and formed a continuous monolayer with 3486 +/- 53 cells/mm(2) cell density. Like normal corneal endothelial cells, the cCCECs were almost hexagonal, squamous, and uniform in size. After transplantation, most cells were vital and functional nearly enough to maintain corneal graft thickness and transparency without rejection for at least 6 weeks. Six weeks after operation, the average thickness of the transplanted corneal grafts was only slightly greater than that before operation. Compared with that in vitro, after transplantation there was 5% to 8% reduction per week in cell density, which lasted for almost 3 weeks. After that, the average cCCEC density of corneal grafts was 2837 +/- 57 cells/mm(2) and quite stable maintained.This study demonstrated that BMHAM would be an ideal alternative for corneal Descemet membrane and a cell carrier for cCCEC transplantation.

At present, guinea pigs have been increasingly used for the study of human myopia. However, little is known about involvement of genetics, protein profiles and key molecules in axial growth of the guinea pig eyes in normal and manipulated visual conditions. This study evaluated the suitability of guinea pigs as an animal model for the study of human refractive errors based on comparison with other currently available species. Various aspects of guinea pigs as an animal model have been researched in this study including the development of refraction and axial components of the guinea pig eye under a normal visual environment, genetic profiles of the guinea pig eye compared with human and mouse eyes, changes in protein profiles, refraction and axial components of the eye during myopic development and recovery (after termination of form deprivation or hyperopic defocus) in response to manipulated visual environments and pharmacological intervention using subconjunctival injection of apomorphine, a non-selective dopamine receptor agonist. Guinea pigs had baseline ocular biometry comparable to humans under a normal visual environment and had similar process of emmetropization compared to humans. Moreover, guinea pigs appeared to be closer to humans than mice based on the ocular gene profiles. Axial myopia induced in guinea pigs was effective. The myopia and recovery were mainly due to changes in vitreous length and choroidal thickness. In respect of pharmacological intervention, a subconjunctival injection of apomorphine could inhibit form-deprivation myopia by slowing axial elongation of the eye in guinea pigs. This study evaluated this myopic animal model comprehensively at the phenotypic genetic and proteomic levels. Guinea pigs are now only the second small animal with detailed gene and protein changes compared to humans. This study the first to use a pharmacological model with detailed dose response curves. Based on the evidence obtained guinea pigs an alternative to other currently available species for the study of the development of human refractive errors.