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JOURNAL ARTICLE
RESEARCH SUPPORT, NON-U.S. GOV'T
Safety evaluation and pharmacodynamics of minocycline hydrochloride eye drops.
Molecular Vision 2022
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 (IC50 ). The safety of Mino eye drops was evaluated on Sprague-Dawley (SD) rat eyes by slit-lamp examination, electroretinography (ERG), histology, and TUNEL assay. Eye drops (1 mg/ml) were applied to the streptozotocin-induced diabetic SD rats. Clinical observations, ERG analyses, and optical coherence tomography analyses were performed monthly for five months. Eyes were then analyzed via histology, blood-retinal barrier function assay, and retinal vascular staining.
RESULTS: Cytotoxicity analysis using HCECs revealed that the IC50 was 250 µg/ml. Safety analyses in healthy SD rats showed that Mino eye drops did not demonstrate any ocular toxicity. Pharmacodynamics analysis showed that retinal thickness at three months was greater in the Mino group than in the non treated (NT) group. The peak times and amplitudes of each program were better in the Mino group than in the NT group at each time point by ERG analyses. Histology examinations showed a thinner ganglion cell layer, fewer ganglion cells, and more dilated blood vessels in the NT group than in the Mino group.
CONCLUSION: Mino eye drops at 1 mg/ml were safe when used in SD rats. Mino eye drops can protect the retina from the development or progression of diabetic retinopathy.
METHODS: Various concentrations of Mino were applied to human corneal epithelial cells (HCECs) to determine the half maximal inhibitory concentration (IC50 ). The safety of Mino eye drops was evaluated on Sprague-Dawley (SD) rat eyes by slit-lamp examination, electroretinography (ERG), histology, and TUNEL assay. Eye drops (1 mg/ml) were applied to the streptozotocin-induced diabetic SD rats. Clinical observations, ERG analyses, and optical coherence tomography analyses were performed monthly for five months. Eyes were then analyzed via histology, blood-retinal barrier function assay, and retinal vascular staining.
RESULTS: Cytotoxicity analysis using HCECs revealed that the IC50 was 250 µg/ml. Safety analyses in healthy SD rats showed that Mino eye drops did not demonstrate any ocular toxicity. Pharmacodynamics analysis showed that retinal thickness at three months was greater in the Mino group than in the non treated (NT) group. The peak times and amplitudes of each program were better in the Mino group than in the NT group at each time point by ERG analyses. Histology examinations showed a thinner ganglion cell layer, fewer ganglion cells, and more dilated blood vessels in the NT group than in the Mino group.
CONCLUSION: Mino eye drops at 1 mg/ml were safe when used in SD rats. Mino eye drops can protect the retina from the development or progression of diabetic retinopathy.
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