Apoptosis can be triggered by several factors such as cytokines, hormones, virus, or drugs. At the right concentrations, these stimuli lead to the activation of effector caspases that trigger the apoptotic program . UV irradiation has been shown to cause the activation of ATP-sensitive potassium (K(ATP)) channels in affected cells causing a loss of K+ ions and a depolarization of the mitochondrial membrane . Intracellular K+ is importantly linked with the inhibition of caspase, and K+ loss is linked with greater rates of apoptosis . In the cornea specifically, it has been observed that while in vivo cells did not perish following exposure to background doses of UVB, cultured cells did perish when exposed to similar UVB doses . It was found that tear film provided a high amount of K+ ions to the corneal epithelia, ensuring a degree of apoptosis-resistance to the chronically UV-irradiated epithelial cells . This is in contrast with the skin which lacks this excess K+ and instead regularly sees UV-triggered apoptosis in the form of sunburn cells .
3. UV Pathogenesis and Rescue
The failure of DNA repair pathways, particularly NER, typically results in developmental disorders, neurological symptoms, and skin cancers. These conditions arise due to the inability of cells to repair DNA in populations of progenitor cells, noncycling cells, and UV-exposed cells 
. While the disease itself is variable, one common trait unifies all of them: DNA photolesions are not being repaired.
The simplest method to prevent DNA photolesions is the avoidance of UV light, be it sunlight or artificial.
Early work on the failure of UV defense system performed in plants found that a loss of CPD photolyase activity resulted in hypersensitivity to UVB 
. CPD photolyase does not exist in placental mammals, 
. There exist animal models with DNA repair mutations that involve the other NER proteins that target CPD and 6-4PP. A model of systemic ERCC1 deficiency showed polyploidy in the liver and kidney 
. Polyploidy has been positively correlated to cell stress and senescence 
. A mouse model of ERCC1-knockdown in the corneal endothelium of saw decreased cell density in the corneal endothelium 
. Unfortunately, there are no reports of loss-of-function NER mutants specific to the corneal epithelia. Studies in humans looking at the NER expression profiles in Fuch’s endothelial corneal dystrophy (FECD) found that XPC was downregulated in patients that had FECD 
. Although this does not make the cells more vulnerable to UV specifically, it does allow for faster accumulation of DNA lesions, which then lead to pathogenesis.
Because placental mammals lack CPD photolyase due to an evolutionary split, there has been some interest expressing CPD photolyase to potentially provide a much more competent repair enzyme. The photolyase in question is still expressed in marsupials and has been introduced into human cells harvested from an XP patient in an attempt to improve the rate of DNA repair. The marsupial photolyase functioned properly in the host cells and did improve survival of human cells following UV irradiation 
. Similar experiments that used microinjections of purified photolyases from yeast also found that UV-mediated cell death was reduced, but to a lesser degree compared to the marsupial photolyase 
. It was hypothesized that the yeast photolyase is not trafficked into the nucleus to the same degree as the marsupial photolyase. With such evidence, work continued with CPD photolyase introduction into placental mammals and a mouse line was generated that ubiquitously expressed either Potorous tridactylus CPD photolyase, Arabidopsis thaliana 6-4PP photolyase, or both 
. The photoreactivation of CPD photolyase resulted in a markedly improved survival of UV-exposed cells in the mice, while photoreactivation of 6-4PPs did not noticeably affect UV-resistance. It should be noted that rodent cells have been documented multiple times as having CPD repair systems less effective than human CPD repair equivalents 
. This lead to research on the introduction of CPD photolyase into mouse models and showed great improvement in recovery from UV damage 
Further work on repair of CPDs in human cells used an mRNA transfection system to express the marsupial Potorous tridactylus CPD photolyase in UVB-irradiated human epidermal keratinocytes. Results showed greatly reduced CPD amount and reduced activation of UV-induced cytokine such as IL-6 
. Use of this system also lead to the identification of which genes where more highly expressed in the presence of CPDs, and thus could be targeted by therapeutic approaches 
. Cell cycle controllers like cyclin E1 and p15INK4b were expressed in greater quantities following JNK activation by UVB exposure. Several other genes were also identified with UV-dependent expression, although it is uncertain how beneficial the expression of each gene is 
. Work on the UV-induced CPD-dependent and CPD-independent cellular mechanisms continues, with CPD photolyase as a major tool. The obvious potential of CPD photolyase as a therapeutic agent in humans has been applied, usually with skin in mind 
. The potential of CPD photolyase in corneal healing comparatively sees less investigation, possibly due to the corneas greater success in dealing with CPDs with existing repair mechanisms or by simply changing the lifestyle of affected patients to better avoid UV exposure.