Disease Information

General Information of the Disease (ID: DIS00118)

Name	Retinopathy
ICD	ICD-11: 9B71

Type(s) of Resistant Mechanism of This Disease

UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Drug

Approved Drug(s)

2 drug(s) in total

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Insulin

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Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
Unusual Activation of Pro-survival Pathway (UAPP)		Click to Show/Hide
Key Molecule: Parkinson disease protein 7 homolog (PARK7)			[1]
Sensitive Disease	Diabetic retinopathy [ICD-11: 9B71.0]
Molecule Alteration	Expression	Up-regulation	Molecule Info
Sensitive Drug	Insulin		Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis	Inhibition	hsa04210
	Nrf2 signaling pathway	Inhibition	hsa05208
Experiment for Molecule Alteration	Western blotting analysis
Experiment for Drug Resistance	TUNEL staining assay
Mechanism Description	After DJ-1 overexpression, apoptosis of rat retinal pericytes (RRPs) decreased, the ratio of B-cell lymphoma-2 (Bcl-2) to BCL2-Associated X Protein (BAX) increased, the production of ROS decreased, and the protein expression and activity of manganese superoxide dismutase (MnSOD, also called SOD2) and catalase (CAT) increased. DJ-1 overexpression activated Nrf2 expression, however, after Nrf2 silencing, apoptosis of RRPs increased, the ratio of Bcl-2 to BAX decreased, the production of ROS increased, the protein expression of MnSOD and CAT decreased, and the expression of heme oxygenase-1 (HO-1), NADP(H) quinone oxidoreductase (NQO1), glutamate-cysteine ligase catalytic subunit (GCLC) and modifier subunit (GCLM) decreased.

Metformin

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Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
Unusual Activation of Pro-survival Pathway (UAPP)		Click to Show/Hide
Key Molecule: Parkinson disease protein 7 homolog (PARK7)			[1]
Sensitive Disease	Diabetic retinopathy [ICD-11: 9B71.0]
Molecule Alteration	Expression	Up-regulation	Molecule Info
Sensitive Drug	Metformin		Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis	Inhibition	hsa04210
	Nrf2 signaling pathway	Inhibition	hsa05208
Experiment for Molecule Alteration	Western blotting analysis
Experiment for Drug Resistance	TUNEL staining assay
Mechanism Description	After DJ-1 overexpression, apoptosis of rat retinal pericytes (RRPs) decreased, the ratio of B-cell lymphoma-2 (Bcl-2) to BCL2-Associated X Protein (BAX) increased, the production of ROS decreased, and the protein expression and activity of manganese superoxide dismutase (MnSOD, also called SOD2) and catalase (CAT) increased. DJ-1 overexpression activated Nrf2 expression, however, after Nrf2 silencing, apoptosis of RRPs increased, the ratio of Bcl-2 to BAX decreased, the production of ROS increased, the protein expression of MnSOD and CAT decreased, and the expression of heme oxygenase-1 (HO-1), NADP(H) quinone oxidoreductase (NQO1), glutamate-cysteine ligase catalytic subunit (GCLC) and modifier subunit (GCLM) decreased.

References

Ref 1	DJ-1 protects retinal pericytes against high glucose-induced oxidative stress through the Nrf2 signaling pathway. Sci Rep. 2020 Feb 12;10(1):2477. doi: 10.1038/s41598-020-59408-2.