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Live/dead staining of HCECs after co-culture with various concentrations of minocycline hydrochloride (Mino) for 24 h. Green staining indicates calcein-AM, and red staining indicates propidium iodide (PI). Scale bar: 100 μm.
Source publication
Purpose:
This study evaluated the safe dosage of minocycline hydrochloride (Mino) eye drops and investigated the potential for the prevention or reduction of retinal damage in a diabetic rat model.
Methods:
Various concentrations of Mino were applied to human corneal epithelial cells (HCECs) to determine the half maximal inhibitory concentration...
Context in source publication
Citations
... [29][30][31][32][33][34] Most notably, minocycline eye drops (1 mg/mL) were safe and effective in a rat model of diabetic retinopaty. 35 However, the antimicrobial action of minocycline can cause problematic side effects, contribute to antimicrobial resistance, and devastate microbiota, particularly with long-term use and systemic administration. 26,[36][37][38] In this study, two hypotheses were tested to reduce potential side effects of minocycline: (1) targeted administration of minocycline via topical eye drops would be efficacious to treat CNV, and (2) modification of minocycline to remove the antimicrobial action, thereby generating a novel modified minocycline analogue, diacetyl minocycline (DAM; also delivered via eye drops), would treat CNV as well as minocycline. ...
... Fluorescein angiography and optical coherence tomography are alternative methods that have been used to evaluate pathologic neovascularization in rodents. 35,39 However, fluorescein angiography can show incompetent blood vessels, and nonperfused vessels cannot be visualized. 39 While optical coherence tomography is a suitable alternative and has been used in similar studies, 35 laser-induced CNV with immunostaining and confocal microscopy was selected because it allows for high-resolution visualization and quantification of microscopic, newly formed blood vessels. ...
... 35,39 However, fluorescein angiography can show incompetent blood vessels, and nonperfused vessels cannot be visualized. 39 While optical coherence tomography is a suitable alternative and has been used in similar studies, 35 laser-induced CNV with immunostaining and confocal microscopy was selected because it allows for high-resolution visualization and quantification of microscopic, newly formed blood vessels. 39,40 Little is known about the safety of targeted administration of minocycline to the eye. ...
Purpose
To evaluate the efficacy of minocycline and a novel, modified minocycline analogue that lacks antimicrobial action, diacetyl minocycline (DAM), on choroidal neovascularization (CNV) in mice of both sexes.
Methods
CNV was induced via laser injury in female and male C57BL/6J mice. Minocycline, DAM, or saline was administered via topical eye drops twice a day for 2 weeks starting the day after laser injury. CNV volume was measured using immunohistochemistry labeling and confocal microscopy.
Results
Minocycline reduced lesion volume by 79% (P ≤ 0.0004) in female and male mice. DAM reduced lesion volume by 73% (P ≤ 0.001) in female and male mice. There was no significant difference in lesion volume between minocycline and DAM treatment groups or between female and male mice.
Conclusions
Both minocycline and DAM eye drops significantly reduced laser-induced CNV lesion volume in female and male mice. While oral tetracyclines have been shown to mitigate pathologic neovascularization in both preclinical studies and clinical trials, the present data are the first to suggest that tetracycline derivatives may be effective to reduce pathologic CNV when administered via topical eye drops. However, the action is unrelated to antimicrobial action. Targeted delivery of these medications via eye drops may reduce the potential for systemic side effects.
Translational Relevance
Topical administration of minocycline and/or DAM via eye drops may represent a novel therapeutic strategy for disorders involving pathologic CNV.
... Therefore, our study proves that HDAC7 promotes the proliferation of HRMECs. Long-term diabetes causes ocular tissue ischemia and hypoxia, which will induce the up-regulation of VEGF factor [32][33] . VEGF induces multiple inflammatory releases and neovascularization through a variety of pathways, such as NF-κB and STAT3 [34][35] . ...
Aim:
To investigate the expression and effect of histone deacetylase 7 (HDAC7) in human retinal microvascular endothelial cells (HRMECs) under high glucose condition and related mechanism, and the expression of HDAC7 in the retinal tissue in diabetic rats.
Methods:
The expression of HDAC7 in HRMECs under high glucose and the retinal tissue from normal or diabetic rats were detected with immunohistochemistry and Western blot. LV-shHDAC7 HRMECs were used to study the effect of HDAC7 on cell activities. Cell count kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU), flow cytometry, scratch test, Transwell test and tube formation assay were used to examine the ability of cell proliferation, migration, and angiogenesis. Finally, a preliminary exploration of its mechanism was performed by Western blot.
Results:
The expression of HDAC7 was both up-regulated in retinal tissues of diabetic rats and high glucose-treated HRMECs. Down-regulation of HDAC7 expression significantly reduced the ability of proliferation, migration, and tube formation, and reversed the high glucose-induced high expression of CDK1/Cyclin B1 and vascular endothelial growth factor in high glucose-treated HRMECs.
Conclusion:
High glucose can up-regulate the expression of HDAC7 in HRMECs. Down-regulation of HDAC7 can inhibit HRMECs activities. HDAC7 is proposed to be involved in pathogenesis of diabetic retinopathy and a therapeutic target.
