Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P05412 (c-Jun)
 11,453 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neovascularization (NV) of the normally avascular cornea arises from various causes including inflammation, infection, trauma, and contact lens wear. Corneal NV, whatever the cause, impairs vision and threatens the survival of corneal allografts, thus representing a serious clinical problem for which treatment is limited. Recent interest has focused on vascular endothelial growth factor (VEGF), a key angiogenic factor whose role in corneal NV is amply documented. While experimental studies underscore the efficacy of anti-VEGF targeted agents, there exists no clear consensus on the ideal treatment for this multifaceted pathology. This review discusses the therapeutic potential of CD36, a well established anti-angiogenic receptor. We present evidence that CD36 contributes significantly to the maintenance of corneal avascularity wherein its deficiency leads to age-related corneal NV. Data further reveal that activation of CD36 substantially attenuates and induces regression of inflammatory corneal NV via concerted inhibition of VEGFA, c-Jun N terminal kinase-1, and c-Jun. In parallel studies, we demonstrate that hypoxia, a fundamental stimulus of NV, markedly elevates CD36 corneal expression in a hypoxia-inducible factor-1 and reactive oxygen species dependent manner. Collectively, our findings unveil interesting avenues for future research on the involvement of CD36 in neovascular eye disease and suggest CD36 agonists as potential therapeutic agents for the management of corneal NV, possibly in combination with anti-VEGF therapies.
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PMID:Emerging roles for the CD36 scavenger receptor as a potential therapeutic target for corneal neovascularization. 1907 79

Aldose reductase (AR) is thought to play a role in the pathogenesis of diabetic eye diseases, including cataract and retinopathy. However, not all diabetics develop ocular complications. Paradoxically, some diabetics with poor metabolic control appear to be protected against retinopathy, while others with a history of excellent metabolic control develop severe complications. These observations indicate that one or more risk factors may influence the likelihood that an individual with diabetes will develop cataracts and/or retinopathy. We hypothesize that an elevated level of AR gene expression could confer higher risk for development of diabetic eye disease. To investigate this hypothesis, we examined the onset and severity of diabetes-induced cataract in transgenic mice, designated AR-TG, that were either heterozygous or homozygous for the human AR (AKR1B1) transgene construct. AR-TG mice homozygous for the transgene demonstrated a conditional cataract phenotype, whereby they developed lens vacuoles and cataract-associated structural changes only after induction of experimental diabetes; no such changes were observed in AR-TG heterozygotes or nontransgenic mice with or without experimental diabetes induction. We observed that nondiabetic AR-TG mice did not show lens structural changes even though they had lenticular sorbitol levels almost as high as the diabetic AR-TG lenses that showed early signs of cataract. Over-expression of AR led to increases in the ratio of activated to total levels of extracellular signal-regulated kinase (ERK1/2) and c-Jun N-terminal (JNK1/2), which are known to be involved in cell growth and apoptosis, respectively. After diabetes induction, AR-TG but not WT controls had decreased levels of phosphorylated as well as total ERK1/2 and JNK1/2 compared to their nondiabetic counterparts. These results indicate that high AR expression in the context of hyperglycemia and insulin deficiency may constitute a risk factor that could predispose the lens to disturbances in signaling through the ERK and JNK pathways and thereby alter the balance of cell growth and apoptosis that is critical to lens transparency and homeostasis.
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PMID:Aldose reductase expression as a risk factor for cataract. 2554 68