Oxidative stress due to vitamin C deficiency has been implicated as critical pathogenic factors contributing to the etiology of retinal and choroidal diseases(10). A cumulative research has focused on the protection of retinal and choroidal physiology and function by vitamin C supplementation due to its antioxidative properties. In our current study, we found that both the retinal and choroidal thickness significantly decreased in the vitamin C deficiency group compared with age- and gender- matched normal vitamin C individuals. This result might suggest a close correlation between vitamin C deficiency with the retinal and choroidal diseases.
An imbalance between ROS and antioxidants in the body may result in excessive generation of ROS, including hydrogen peroxide, superoxide and peroxynitrate. These insults may damage cellular macromolecules and organelles and promote cell death via apoptosis. Vitamin C is an important antioxidant which can prevent the oxidative damage to the retina(13). A high level of vitamin C in retina alleviates free radicals and improves immune cell function generated by its high metabolic activity(9). As a result, there has been persistent interest in antioxidant approaches (such as vitamin C) to combat oxidative stress in retinal diseases.
The retina and choroid possess a high-affinity transport system for vitamin C and the highest concentration of vitamins was located in the RPE followed by the outer segments of the photoreceptor cells(14). Both in vivo and in vitro experiments have verified the prominent effect of vitamin C in retina health(14). In animal model of vitamin C deficiency, short-term low vitamin C level would induce oxidative stress in the retinas of young guinea pigs(15, 16). In a model of porcine hypercholesterolemia, vitamins C improved retinal structure alteration in transmission electron microscopy by preventing oxidative stress and nitric oxide metabolites(17). In an oxidative stress model induced by hydrogen peroxide and ultraviolet B irradiation of ARPE-19 cells, antioxidative effect of vitamin C could result in increment in cell viability and reduction in intracellular ROS level(18). The study of AREDS showed that treatment of high dose antioxidant supplements in patients with intermediate AMD was effective in retarding the progression of AMD compared with placebo(19, 20).
Mechanisms by which vitamin C deficiency correlated with retinal and choroidal thickness are multifactorial. Vitamin C deficiency may increase oxidative stress which directly contributes to apoptosis, damaging of retina cells (especially the photoreceptor cell) and activation of retinal immune system. The decrease of retinal thickness may due to the thinning of the photoreceptor cell layer caused by apoptosis, shortening of the photoreceptor cell outer segment. In an animal study, spaceflight inducing oxidative damage resulted an increase in photoreceptor cone damage, and reduction of thickness of the retinal outer nuclear layer (ONL), retinal inner nuclear layer (INL), RPE, and choroid layers of the eye in C57BL/6 mice(21). In retinal glial cells, oxidative stress increased the expression of major histocompatibility complex (MHC) II, consequently improving the ability to stimulate T cell proliferation and secretion of cytokines (TNFa) that can induce glial cell apoptosis(22). As the cones contain more mitochondria and have a higher energy demand than rods, it is much more prone to be affected by oxidative stress(23). In our study, the center and the inner sectors of the retina showed the most significant difference between the two groups, while the outer sectors had a trend of retinal thinning without significant difference.
The second possibility was role of vitamin C in the function of vascular endothelium(24). Ascorbate has long been known to enhance endothelial synthesis and deposition of Type IV collagen to form the basement membrane of blood vessels. Cell experiment demonstrated that vitamin C could tighten the endothelial permeability barrier and control endothelial cell proliferation and apoptosis resulting from many dioxygenase involved in endothelial function, proliferation, and survival(24). Recent studies have found that low vitamin C concentration is linked with vascular disease, such as atherosclerosis and cardiovascular diseases due to endothelial dysfunction(25, 26). High dose of vitamin C administration showed beneficial function in endothelial function in various artery diseases(27, 28).
Moreover, vitamin C is closely associated with inflammatory regulation. A cumulative researches have confirmed that inflammation is a critical factor contributing to the pathogenesis of many microvascular disorders(29, 30). Retinal and choroidal thickness showed close relation with inflammatory diseases (31). Balmforth et al. revealed a choroidal thinning with increased IL-6, TNF-α and endothelin-1 due to inflammation and endothelial dysfunction(32). These might be the reasons contributing to the significant difference in retinal and choroidal thickness between the two groups.
Although the retina is extremely sensitive to oxidative stress, retinal thickness in the vitamin C deficiency does not have such a remarkable thinning as the choroidal thickness. The possible explanation is the high blood flow of choroidal vasculature compared with retina vessels. Moreover, regulation of blood flow to the retina and the choroid is quite different: retinal flow vasculature can accommodate autogenously, while choroidal flow relies on autonomic regulation.
The present study has several limitations. First, although we have included 100 individuals, we still need a larger population to evaluate the effect of vitamin C in choroidal and retinal vasculature. Secondly, we did not assess the smoking population among the subjects while cigarette was believed to be partially responsible for choroid thinning. Future prospective studies of serum antioxidants and incident of retina and choroid thinning may help to further clarify the effect of antioxidants on the health of retina and choroid.