Table 1.
Selected studies on the relationship between DJ-1 inducer/suppressor and ocular diseases
| Ocular Disease | Type | Models | Results | Reference |
|---|---|---|---|---|
| FECD | In vitro | Human corneal endothelial cell lines | SFN enhanced nuclear translocation of Nrf2 in human FECD specimens under tBHP induced oxidative stress and led to increased DJ-1 synthesis. | 20 |
| In vitro | CECs from ex vivo corneas of DJ-1 knockout mice | DJ-1-deficient CECs exhibited the vulnerable response to UV-A irradiation, and the decline in DJ-1 led to activation of caspase-3 and phospho-p53 under the oxidative stress, which plays a central role in the execution-phase of cell apoptosis. DJ-1 may serve a protective role against UV-A-induced apoptosis by inhibiting phospho-53-mediated apoptosis pathway. |
19 | |
| AMD | In vivo | DJ-1 KO mice | DJ-1 is a protecting factor for RPE/photoreceptors against the oxidative stress (such as aging) by regulating Nrf2 signaling and DJ-1 may serve as a potential target for the prevention of the geographic atrophy and vision loss in AMD. | 21, 22 |
| Cataracts | In vivo | cataractous human lens; glutathione-depleted mouse | Cys46 and Cys53 were found to be oxidized in aged cataractous human lens and glutathione-depleted mouse. The oxidation of DJ-1 protein was closely related to disulfide cross-linking. |
25. |
| ocular neurodegenerative diseases | In vivo | Nrf2 KO mice | RGC apoptosis is considerably increased in Nrf2 KO mice, and gene therapy with Nrf2 can reduce RGC death. DJ-1 can stabilize Nrf2 and induce the expression of antioxidant thioredoxin 1 through the Nrf2 pathway. |
41. |
| In vitro | Mouse NIH3T3 cells | Activation of the PI3K/Akt pathway is often induced by substances able to prevent RGC death in retinal ischemia. DJ-1 activated PI3K/Akt pathway and exhibited its cytoprotective role via the inhibition of PTEN. |
47, 48 | |
| In vivo | mice model of glaucoma | ASK1 deletion prevented RGC apoptosis and increased RGC survival in mice model of glaucoma. | 53 | |
| In vitro | mouse embryonic fibroblast | DJ-1 can bind with ASK1 via the Cys-106 under oxidative stress. | 54 | |
| UM | In vitro | UM cell lines | DJ-1 protein could be secreted into the bloodstream by both UM-A and other UM cell lines cultured in vitro, but not by normal melanocytes, indicating that DJ-1 protein may serve as a potential serum marker for UM. | 65 |
Abbreviations: FECD, Fuchs endothelial corneal dystrophy; SFN, Sulforaphane; AMD, Age-related macular degeneration; Nrf2, Nuclear factor erythroid 2-related factor 2; tBHP, tert-Butyl hydroperoxide; CECs, corneal endothelial cells; PI3K, phosphoinositide 3-kinase; RGC, retinal ganglion cells; PTEN, Phosphatase and Tensin homolog deleted on chromosome 10; ASK1, Apoptosis signal-regulating kinase 1; UM, uveal melanoma