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Minocycline inhibits PARP‑1 expression and decreases apoptosis in diabetic retinopathy.

Wu Y, Chen Y, Wu Q, Jia L, Du X - Mol Med Rep (2015)

Bottom Line: The present study aimed to investigate the mechanism underlying the effects of minocycline on diabetic retinopathy‑associated cellular apoptosis.Following treatment with minocycline, the abnormal expression of PARP‑1 in the retina was inhibited, and cellular apoptosis was decreased.In conclusion, the results of the present study suggest that PARP‑1 is involved in the development of diabetic retinopathy, and minocycline is able to inhibit PARP‑1 expression and decrease cellular apoptosis, suggesting that minocycline may prove to be a promising drug for the treatment of diabetic retinopathy.

View Article: PubMed Central - PubMed

Affiliation: Department of Ultrasound, Shanghai First People's Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200080, P.R. China.

ABSTRACT
The present study aimed to investigate the mechanism underlying the effects of minocycline on diabetic retinopathy‑associated cellular apoptosis. A total of 40 Sprague Dawley (SD) rats were used as a diabetic retinopathy model following injection with streptozotocin. Among the 34 rats in which the diabetes model was successfully established, 24 rats were divided into two experimental groups: I and II (T1 and T2, respectively), and orally administered with various doses of minocycline. The remaining 10 rats served as the diabetic retinopathy control group. An additional group of 10 healthy SD rats with comparable weight served as normal controls. The rats in T1 and T2 groups were treated daily for eight consecutive weeks with minocycline at a dose of 2.5 mg/kg and 5 mg/kg, respectively. The mRNA expression levels of poly (ADP‑ribose) polymerase‑1 (PARP‑1) were subsequently measured by reverse transcription‑quantitative polymerase chain reaction, and the protein expression levels of poly‑ADP‑ribose were measured by western blot analysis and immunohistochemistry. Retinal morphology was observed following hematoxylin and eosin staining, and retinal cell apoptosis was measured by terminal deoxynucleotidyl transferase dUTP nick end labeling and caspase‑3 activity assays. The amplitudes of the electroretinogram (ERG) b‑wave and oscillary potentials (OPs) were measured using visual electrophysiology, and compared among the four groups. The results of the present study demonstrated that in the diabetic rats, retinal PARP‑1 gene expression was markedly upregulated, the number of apoptotic cells and the activity levels of caspase‑3 were increased, and the amplitude of the ERG b‑wave and the OPs were markedly lower as compared with the normal rats. Following treatment with minocycline, the abnormal expression of PARP‑1 in the retina was inhibited, and cellular apoptosis was decreased. In conclusion, the results of the present study suggest that PARP‑1 is involved in the development of diabetic retinopathy, and minocycline is able to inhibit PARP‑1 expression and decrease cellular apoptosis, suggesting that minocycline may prove to be a promising drug for the treatment of diabetic retinopathy.

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The number of apoptotic cells increased significantly following 10 weeks in the DM rats, and decreased following minocycline treatment. (A) A small number of apoptotic cells were present in the rat retinal tissue samples of the CON group. (B) The number of apoptotic cells increased significantly following 10 weeks in the DM rats. The apoptotic cells were located in the GCL, INL and ONL. (C and D) Following minocycline treatment, significantly less apoptotic cells were present in the retinal tissue samples of the DM rats in the T1 and T2 groups. (E) The apoptotic index in the GCL of the DM rats was significantly higher, as compared with the CON group. Following minocycline treatment, the elevated apoptotic index in the GCL of the retinal tissue samples of the DM rats was suppressed (F=53.57; *P<0.01 vs. CON). No significant difference was observed between the GCL apoptotic index of the T1 and T2 treatment groups (**P>0.05). (F) Apoptotic index of the INL of the DM rats was significantly elevated, as compared with the CON group. Following minocycline treatment, the elevated apoptotic index in the INL of the retinal tissue samples of the DM rats was unchanged (F=28.32; *P<0.01 vs. CON). No significant difference was observed between the INL apoptotic index of the T1 and T2 treatment groups (P>0.05). (Scale bars, 25 µm). CON, control group; DM, diabetic retinopathy group; T1, 2.5 mg/kg minocycline treatment group; T2, 5 mg/kg minocycline treatment group; GCL, ganglion cell layer; ONL, outer nuclear layer; INL, inner nuclear layer.
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f3-mmr-12-04-4887: The number of apoptotic cells increased significantly following 10 weeks in the DM rats, and decreased following minocycline treatment. (A) A small number of apoptotic cells were present in the rat retinal tissue samples of the CON group. (B) The number of apoptotic cells increased significantly following 10 weeks in the DM rats. The apoptotic cells were located in the GCL, INL and ONL. (C and D) Following minocycline treatment, significantly less apoptotic cells were present in the retinal tissue samples of the DM rats in the T1 and T2 groups. (E) The apoptotic index in the GCL of the DM rats was significantly higher, as compared with the CON group. Following minocycline treatment, the elevated apoptotic index in the GCL of the retinal tissue samples of the DM rats was suppressed (F=53.57; *P<0.01 vs. CON). No significant difference was observed between the GCL apoptotic index of the T1 and T2 treatment groups (**P>0.05). (F) Apoptotic index of the INL of the DM rats was significantly elevated, as compared with the CON group. Following minocycline treatment, the elevated apoptotic index in the INL of the retinal tissue samples of the DM rats was unchanged (F=28.32; *P<0.01 vs. CON). No significant difference was observed between the INL apoptotic index of the T1 and T2 treatment groups (P>0.05). (Scale bars, 25 µm). CON, control group; DM, diabetic retinopathy group; T1, 2.5 mg/kg minocycline treatment group; T2, 5 mg/kg minocycline treatment group; GCL, ganglion cell layer; ONL, outer nuclear layer; INL, inner nuclear layer.

Mentions: TUNEL imaging demonstrated that a small number of apoptotic cells were present in the rat retinal tissue samples of the CON group (Fig. 3). Following treatment for 10 weeks, the HE staining in the DM rats appeared normal, however the number of apoptotic cells had significantly increased, as compared with the CON group. The apoptotic cells were predominantly located in the GCL and the INL. The apoptotic index of the GCL in the four groups (CON, DM, T1 and T2) was 3.4±1.14, 21.2±3.56, 11.8±2.04, and 10.8±1.30%, respectively. The apoptotic index of the INL was 2.8±0.84, 7.5±1.12, 7.3±0.45, and 6.3±1.10%, respectively. The apoptotic index of the GCL and INL in the DM rats were significantly higher, as compared with the CON group (F=53.57, P<0.01; F=28.32, P<0.01). Following minocycline treatment, the elevated apoptotic index of GCL in the retinal tissue samples of the DM rats was suppressed (F=53.57, P<0.01), whereas the apoptotic index of the INL in the retinal tissue samples of the DM rats was unchanged (P>0.05), as compared with the CON group.


Minocycline inhibits PARP‑1 expression and decreases apoptosis in diabetic retinopathy.

Wu Y, Chen Y, Wu Q, Jia L, Du X - Mol Med Rep (2015)

The number of apoptotic cells increased significantly following 10 weeks in the DM rats, and decreased following minocycline treatment. (A) A small number of apoptotic cells were present in the rat retinal tissue samples of the CON group. (B) The number of apoptotic cells increased significantly following 10 weeks in the DM rats. The apoptotic cells were located in the GCL, INL and ONL. (C and D) Following minocycline treatment, significantly less apoptotic cells were present in the retinal tissue samples of the DM rats in the T1 and T2 groups. (E) The apoptotic index in the GCL of the DM rats was significantly higher, as compared with the CON group. Following minocycline treatment, the elevated apoptotic index in the GCL of the retinal tissue samples of the DM rats was suppressed (F=53.57; *P<0.01 vs. CON). No significant difference was observed between the GCL apoptotic index of the T1 and T2 treatment groups (**P>0.05). (F) Apoptotic index of the INL of the DM rats was significantly elevated, as compared with the CON group. Following minocycline treatment, the elevated apoptotic index in the INL of the retinal tissue samples of the DM rats was unchanged (F=28.32; *P<0.01 vs. CON). No significant difference was observed between the INL apoptotic index of the T1 and T2 treatment groups (P>0.05). (Scale bars, 25 µm). CON, control group; DM, diabetic retinopathy group; T1, 2.5 mg/kg minocycline treatment group; T2, 5 mg/kg minocycline treatment group; GCL, ganglion cell layer; ONL, outer nuclear layer; INL, inner nuclear layer.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4581760&req=5

f3-mmr-12-04-4887: The number of apoptotic cells increased significantly following 10 weeks in the DM rats, and decreased following minocycline treatment. (A) A small number of apoptotic cells were present in the rat retinal tissue samples of the CON group. (B) The number of apoptotic cells increased significantly following 10 weeks in the DM rats. The apoptotic cells were located in the GCL, INL and ONL. (C and D) Following minocycline treatment, significantly less apoptotic cells were present in the retinal tissue samples of the DM rats in the T1 and T2 groups. (E) The apoptotic index in the GCL of the DM rats was significantly higher, as compared with the CON group. Following minocycline treatment, the elevated apoptotic index in the GCL of the retinal tissue samples of the DM rats was suppressed (F=53.57; *P<0.01 vs. CON). No significant difference was observed between the GCL apoptotic index of the T1 and T2 treatment groups (**P>0.05). (F) Apoptotic index of the INL of the DM rats was significantly elevated, as compared with the CON group. Following minocycline treatment, the elevated apoptotic index in the INL of the retinal tissue samples of the DM rats was unchanged (F=28.32; *P<0.01 vs. CON). No significant difference was observed between the INL apoptotic index of the T1 and T2 treatment groups (P>0.05). (Scale bars, 25 µm). CON, control group; DM, diabetic retinopathy group; T1, 2.5 mg/kg minocycline treatment group; T2, 5 mg/kg minocycline treatment group; GCL, ganglion cell layer; ONL, outer nuclear layer; INL, inner nuclear layer.
Mentions: TUNEL imaging demonstrated that a small number of apoptotic cells were present in the rat retinal tissue samples of the CON group (Fig. 3). Following treatment for 10 weeks, the HE staining in the DM rats appeared normal, however the number of apoptotic cells had significantly increased, as compared with the CON group. The apoptotic cells were predominantly located in the GCL and the INL. The apoptotic index of the GCL in the four groups (CON, DM, T1 and T2) was 3.4±1.14, 21.2±3.56, 11.8±2.04, and 10.8±1.30%, respectively. The apoptotic index of the INL was 2.8±0.84, 7.5±1.12, 7.3±0.45, and 6.3±1.10%, respectively. The apoptotic index of the GCL and INL in the DM rats were significantly higher, as compared with the CON group (F=53.57, P<0.01; F=28.32, P<0.01). Following minocycline treatment, the elevated apoptotic index of GCL in the retinal tissue samples of the DM rats was suppressed (F=53.57, P<0.01), whereas the apoptotic index of the INL in the retinal tissue samples of the DM rats was unchanged (P>0.05), as compared with the CON group.

Bottom Line: The present study aimed to investigate the mechanism underlying the effects of minocycline on diabetic retinopathy‑associated cellular apoptosis.Following treatment with minocycline, the abnormal expression of PARP‑1 in the retina was inhibited, and cellular apoptosis was decreased.In conclusion, the results of the present study suggest that PARP‑1 is involved in the development of diabetic retinopathy, and minocycline is able to inhibit PARP‑1 expression and decrease cellular apoptosis, suggesting that minocycline may prove to be a promising drug for the treatment of diabetic retinopathy.

View Article: PubMed Central - PubMed

Affiliation: Department of Ultrasound, Shanghai First People's Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200080, P.R. China.

ABSTRACT
The present study aimed to investigate the mechanism underlying the effects of minocycline on diabetic retinopathy‑associated cellular apoptosis. A total of 40 Sprague Dawley (SD) rats were used as a diabetic retinopathy model following injection with streptozotocin. Among the 34 rats in which the diabetes model was successfully established, 24 rats were divided into two experimental groups: I and II (T1 and T2, respectively), and orally administered with various doses of minocycline. The remaining 10 rats served as the diabetic retinopathy control group. An additional group of 10 healthy SD rats with comparable weight served as normal controls. The rats in T1 and T2 groups were treated daily for eight consecutive weeks with minocycline at a dose of 2.5 mg/kg and 5 mg/kg, respectively. The mRNA expression levels of poly (ADP‑ribose) polymerase‑1 (PARP‑1) were subsequently measured by reverse transcription‑quantitative polymerase chain reaction, and the protein expression levels of poly‑ADP‑ribose were measured by western blot analysis and immunohistochemistry. Retinal morphology was observed following hematoxylin and eosin staining, and retinal cell apoptosis was measured by terminal deoxynucleotidyl transferase dUTP nick end labeling and caspase‑3 activity assays. The amplitudes of the electroretinogram (ERG) b‑wave and oscillary potentials (OPs) were measured using visual electrophysiology, and compared among the four groups. The results of the present study demonstrated that in the diabetic rats, retinal PARP‑1 gene expression was markedly upregulated, the number of apoptotic cells and the activity levels of caspase‑3 were increased, and the amplitude of the ERG b‑wave and the OPs were markedly lower as compared with the normal rats. Following treatment with minocycline, the abnormal expression of PARP‑1 in the retina was inhibited, and cellular apoptosis was decreased. In conclusion, the results of the present study suggest that PARP‑1 is involved in the development of diabetic retinopathy, and minocycline is able to inhibit PARP‑1 expression and decrease cellular apoptosis, suggesting that minocycline may prove to be a promising drug for the treatment of diabetic retinopathy.

Show MeSH
Related in: MedlinePlus