Beneficial Effect of Sirolimus-Pretreated Mesenchymal Stem Cell Implantation on Diabetic Retinopathy in Rats
Background: Diabetic retinopathy (DR) is a vision-threatening complication that affects virtually all diabetic patients. Various treatments have been attempted, but they have many side effects and limitations. Alternatively, stem cell therapy is being actively researched, but it faces challenges due...
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MDPI AG
2024-02-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/12/2/383 |
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| author | Nanyoung Kang Ji Seung Jung Jiyi Hwang Sang-Eun Park Myeongjee Kwon Haerin Yoon Jungyeon Yong Heung-Myong Woo Kyung-Mee Park |
| author_facet | Nanyoung Kang Ji Seung Jung Jiyi Hwang Sang-Eun Park Myeongjee Kwon Haerin Yoon Jungyeon Yong Heung-Myong Woo Kyung-Mee Park |
| author_sort | Nanyoung Kang |
| collection | DOAJ |
| description | Background: Diabetic retinopathy (DR) is a vision-threatening complication that affects virtually all diabetic patients. Various treatments have been attempted, but they have many side effects and limitations. Alternatively, stem cell therapy is being actively researched, but it faces challenges due to a low cell survival rate. In this study, stem cells were pretreated with sirolimus, which is known to promote cell differentiation and enhance the survival rate. Additionally, the subconjunctival route was employed to reduce complications following intravitreal injections. Methods: Diabetes mellitus was induced by intraperitoneal injection of 55 mg/kg of streptozotocin (STZ), and DR was confirmed at 10 weeks after DM induction through electroretinogram (ERG). The rats were divided into four groups: intact control group (INT), diabetic retinopathy group (DR), DR group with subconjunctival MSC injection (DR-MSC), and DR group with subconjunctival sirolimus-pretreated MSC injection (DR-MSC-S). The effects of transplantation were evaluated using ERG and histological examinations. Results: The ERG results showed that the DR-MSC-S group did not significantly differ from the INT in b-wave amplitude and exhibited significantly higher values than the DR-MSC and DR groups (<i>p</i> < 0.01). The flicker amplitude results showed that the DR-MSC and DR-MSC-S groups had significantly higher values than the DR group (<i>p</i> < 0.01). Histological examination revealed that the retinal layers were thinner in the DR-induced groups compared to the INT group, with the DR-MSC-S group showing the thickest retinal layers among them. Conclusions: Subconjunctival injection of sirolimus-pretreated MSCs can enhance retinal function and mitigate histological changes in the STZ-induced DR rat model. |
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| language | English |
| last_indexed | 2024-03-07T22:40:26Z |
| publishDate | 2024-02-01 |
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| series | Biomedicines |
| spelling | doaj.art-2a8cadf003a543149960e4df74f5f6a32024-02-23T15:08:40ZengMDPI AGBiomedicines2227-90592024-02-0112238310.3390/biomedicines12020383Beneficial Effect of Sirolimus-Pretreated Mesenchymal Stem Cell Implantation on Diabetic Retinopathy in RatsNanyoung Kang0Ji Seung Jung1Jiyi Hwang2Sang-Eun Park3Myeongjee Kwon4Haerin Yoon5Jungyeon Yong6Heung-Myong Woo7Kyung-Mee Park8Laboratory of Veterinary Ophthalmology, College of Veterinary Medicine, Chungbuk National University, Cheongju 28644, Republic of KoreaLaboratory of Veterinary Ophthalmology, College of Veterinary Medicine, Chungbuk National University, Cheongju 28644, Republic of KoreaLaboratory of Veterinary Ophthalmology, College of Veterinary Medicine, Chungbuk National University, Cheongju 28644, Republic of KoreaLaboratory of Veterinary Ophthalmology, College of Veterinary Medicine, Chungbuk National University, Cheongju 28644, Republic of KoreaLaboratory of Veterinary Ophthalmology, College of Veterinary Medicine, Chungbuk National University, Cheongju 28644, Republic of KoreaLaboratory of Veterinary Ophthalmology, College of Veterinary Medicine, Chungbuk National University, Cheongju 28644, Republic of KoreaLaboratory of Veterinary Ophthalmology, College of Veterinary Medicine, Chungbuk National University, Cheongju 28644, Republic of KoreaLaboratory of Veterinary Surgery, College of Veterinary Medicine, Kangwon National University, Chuncheon 24341, Republic of KoreaLaboratory of Veterinary Ophthalmology, College of Veterinary Medicine, Chungbuk National University, Cheongju 28644, Republic of KoreaBackground: Diabetic retinopathy (DR) is a vision-threatening complication that affects virtually all diabetic patients. Various treatments have been attempted, but they have many side effects and limitations. Alternatively, stem cell therapy is being actively researched, but it faces challenges due to a low cell survival rate. In this study, stem cells were pretreated with sirolimus, which is known to promote cell differentiation and enhance the survival rate. Additionally, the subconjunctival route was employed to reduce complications following intravitreal injections. Methods: Diabetes mellitus was induced by intraperitoneal injection of 55 mg/kg of streptozotocin (STZ), and DR was confirmed at 10 weeks after DM induction through electroretinogram (ERG). The rats were divided into four groups: intact control group (INT), diabetic retinopathy group (DR), DR group with subconjunctival MSC injection (DR-MSC), and DR group with subconjunctival sirolimus-pretreated MSC injection (DR-MSC-S). The effects of transplantation were evaluated using ERG and histological examinations. Results: The ERG results showed that the DR-MSC-S group did not significantly differ from the INT in b-wave amplitude and exhibited significantly higher values than the DR-MSC and DR groups (<i>p</i> < 0.01). The flicker amplitude results showed that the DR-MSC and DR-MSC-S groups had significantly higher values than the DR group (<i>p</i> < 0.01). Histological examination revealed that the retinal layers were thinner in the DR-induced groups compared to the INT group, with the DR-MSC-S group showing the thickest retinal layers among them. Conclusions: Subconjunctival injection of sirolimus-pretreated MSCs can enhance retinal function and mitigate histological changes in the STZ-induced DR rat model.https://www.mdpi.com/2227-9059/12/2/383diabetic retinopathysirolimusmesenchymal stem cellssubconjunctival injection |
| spellingShingle | Nanyoung Kang Ji Seung Jung Jiyi Hwang Sang-Eun Park Myeongjee Kwon Haerin Yoon Jungyeon Yong Heung-Myong Woo Kyung-Mee Park Beneficial Effect of Sirolimus-Pretreated Mesenchymal Stem Cell Implantation on Diabetic Retinopathy in Rats Biomedicines diabetic retinopathy sirolimus mesenchymal stem cells subconjunctival injection |
| title | Beneficial Effect of Sirolimus-Pretreated Mesenchymal Stem Cell Implantation on Diabetic Retinopathy in Rats |
| title_full | Beneficial Effect of Sirolimus-Pretreated Mesenchymal Stem Cell Implantation on Diabetic Retinopathy in Rats |
| title_fullStr | Beneficial Effect of Sirolimus-Pretreated Mesenchymal Stem Cell Implantation on Diabetic Retinopathy in Rats |
| title_full_unstemmed | Beneficial Effect of Sirolimus-Pretreated Mesenchymal Stem Cell Implantation on Diabetic Retinopathy in Rats |
| title_short | Beneficial Effect of Sirolimus-Pretreated Mesenchymal Stem Cell Implantation on Diabetic Retinopathy in Rats |
| title_sort | beneficial effect of sirolimus pretreated mesenchymal stem cell implantation on diabetic retinopathy in rats |
| topic | diabetic retinopathy sirolimus mesenchymal stem cells subconjunctival injection |
| url | https://www.mdpi.com/2227-9059/12/2/383 |
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