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) 3 drug(s) in total

Idebenone

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Ubiquitin-like modifier-activating enzyme ATG7 (ATG7) [1]

• Sensitive Disease: Diabetic retinopathy [ICD-11: 9B71.0]
• Sensitive Drug: Idebenone
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: PI3K signaling pathway; Regulation; N.A.
• Cell Pathway Regulation: Akt signaling pathway; Regulation; N.A.
• In Vitro Model: RF/6A cells; Chorioretinal; Homo sapiens (Human); CVCL_4552
• In Vivo Model: Diabetic rats model; Rattus norvegicus
• Experiment for Molecule Alteration: Western blot assay
• Experiment for Drug Resistance: Ocular fundus ultrasound testing; Histological assay; Cell proliferation assay
• Mechanism Description: IDE regulated the autophagy of retina cells to alleviate diabetic retinopathy via regulating the PI3K signaling pathway.The PI3K/Akt/mTOR signaling pathway acts as the mediator of IDE in alleviating DR.IDE treatment suppressed the activation of the PI3K/Akt/mTOR signaling pathway, and PI3K signaling repressed the protective role of IDE in DR, explaining the IDE-suppressed autophagy in DR.

Key Molecule: Apoptosis regulator Bcl-2 (BCL2) [1]

• Sensitive Disease: Diabetic retinopathy [ICD-11: 9B71.0]
• Sensitive Drug: Idebenone
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: PI3K signaling pathway; Regulation; N.A.
• Cell Pathway Regulation: Akt signaling pathway; Regulation; N.A.
• In Vitro Model: RF/6A cells; Chorioretinal; Homo sapiens (Human); CVCL_4552
• In Vivo Model: Diabetic rats model; Rattus norvegicus
• Experiment for Molecule Alteration: Western blot assay
• Experiment for Drug Resistance: Ocular fundus ultrasound testing; Histological assay; Cell proliferation assay
• Mechanism Description: IDE regulated the autophagy of retina cells to alleviate diabetic retinopathy via regulating the PI3K signaling pathway.The PI3K/Akt/mTOR signaling pathway acts as the mediator of IDE in alleviating DR.IDE treatment suppressed the activation of the PI3K/Akt/mTOR signaling pathway, and PI3K signaling repressed the protective role of IDE in DR, explaining the IDE-suppressed autophagy in DR.

Key Molecule: BCL2 associated X protein (BAX) [1]

• Sensitive Disease: Diabetic retinopathy [ICD-11: 9B71.0]
• Sensitive Drug: Idebenone
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: PI3K signaling pathway; Regulation; N.A.
• Cell Pathway Regulation: Akt signaling pathway; Regulation; N.A.
• In Vitro Model: RF/6A cells; Chorioretinal; Homo sapiens (Human); CVCL_4552
• In Vivo Model: Diabetic rats model; Rattus norvegicus
• Experiment for Molecule Alteration: Western blot assay
• Experiment for Drug Resistance: Ocular fundus ultrasound testing; Histological assay; Cell proliferation assay
• Mechanism Description: IDE regulated the autophagy of retina cells to alleviate diabetic retinopathy via regulating the PI3K signaling pathway.The PI3K/Akt/mTOR signaling pathway acts as the mediator of IDE in alleviating DR.IDE treatment suppressed the activation of the PI3K/Akt/mTOR signaling pathway, and PI3K signaling repressed the protective role of IDE in DR, explaining the IDE-suppressed autophagy in DR.

Key Molecule: Beclin-1 (BECN1) [1]

• Sensitive Disease: Diabetic retinopathy [ICD-11: 9B71.0]
• Sensitive Drug: Idebenone
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: PI3K signaling pathway; Regulation; N.A.
• Cell Pathway Regulation: Akt signaling pathway; Regulation; N.A.
• In Vitro Model: RF/6A cells; Chorioretinal; Homo sapiens (Human); CVCL_4552
• In Vivo Model: Diabetic rats model; Rattus norvegicus
• Experiment for Molecule Alteration: Western blot assay
• Experiment for Drug Resistance: Ocular fundus ultrasound testing; Histological assay; Cell proliferation assay
• Mechanism Description: IDE regulated the autophagy of retina cells to alleviate diabetic retinopathy via regulating the PI3K signaling pathway.The PI3K/Akt/mTOR signaling pathway acts as the mediator of IDE in alleviating DR.IDE treatment suppressed the activation of the PI3K/Akt/mTOR signaling pathway, and PI3K signaling repressed the protective role of IDE in DR, explaining the IDE-suppressed autophagy in DR.

Insulin

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Parkinson disease protein 7 homolog (PARK7) [2]

• Sensitive Disease: Diabetic retinopathy [ICD-11: 9B71.0]
• Sensitive Drug: Insulin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Nrf2 signaling pathway; Inhibition; hsa05208
• Experiment for Molecule Alteration: Western blot 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

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Parkinson disease protein 7 homolog (PARK7) [2]

• Sensitive Disease: Diabetic retinopathy [ICD-11: 9B71.0]
• Sensitive Drug: Metformin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Nrf2 signaling pathway; Inhibition; hsa05208
• Experiment for Molecule Alteration: Western blot 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: Idebenone Attenuates Diabetic Retinopathy by Modulating Autophagy Via Targeting Akt Signaling. Curr Med Chem. 2024 Nov 1.
• Ref 2: 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.