Intraocular Pressure-Lowering and Retina-Protective Effects of Exosome-Rich Conditioned Media from Human Amniotic Membrane Stem Cells in a Rat Model of Glaucoma
Glaucoma is one of the most devastating eye diseases, since the disease can develop into blindness and no effective therapeutics are available. Although the exact mechanisms and causes of glaucoma are unknown, increased intraocular pressure (IOP) has been demonstrated to be an important risk factor....
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MDPI AG
2023-04-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/9/8073 |
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| author | Hye-Rim Seong Chan Ho Noh Sangryong Park Sumin Cho Seok-Jin Hong Ah-young Lee Dongho Geum Soon-Cheol Hong Dongsun Park Tae Myoung Kim Ehn-Kyoung Choi Yun-Bae Kim |
| author_facet | Hye-Rim Seong Chan Ho Noh Sangryong Park Sumin Cho Seok-Jin Hong Ah-young Lee Dongho Geum Soon-Cheol Hong Dongsun Park Tae Myoung Kim Ehn-Kyoung Choi Yun-Bae Kim |
| author_sort | Hye-Rim Seong |
| collection | DOAJ |
| description | Glaucoma is one of the most devastating eye diseases, since the disease can develop into blindness and no effective therapeutics are available. Although the exact mechanisms and causes of glaucoma are unknown, increased intraocular pressure (IOP) has been demonstrated to be an important risk factor. Exosomes are lipid nanoparticles secreted from functional cells, including stem cells, and have been found to contain diverse functional molecules that control body function, inhibit inflammation, protect and regenerate cells, and restore damaged tissues. In the present study, exosome-rich conditioned media (ERCMs) were attained via hypoxic culture (2% O<sub>2</sub>) of human amniotic membrane mesenchymal stem cells (AMMSCs) and amniotic membrane epithelial stem cells (AMESCs) containing 50 times more exosome particles than normoxic culture (20% O<sub>2</sub>) medium (NCM). The exosome particles in ERCM were confirmed to be 77 nm in mean size and contain much greater amounts of growth factors (GFs) and neurotrophic factors (NFs) than those in NCM. The glaucoma-therapeutic effects of ERCMs were assessed in retinal cells and a hypertonic (1.8 M) saline-induced high-IOP animal model. CM-DiI-labeled AMMSC exosomes were found to readily penetrate the normal and H<sub>2</sub>O<sub>2</sub>-damaged retinal ganglion cells (RGCs), and AMMSC-ERCM not only facilitated retinal pigment epithelial cell (RPEC) proliferation but also protected against H<sub>2</sub>O<sub>2</sub>- and hypoxia-induced RPEC insults. The IOP of rats challenged with 1.8 M saline increased twice the normal IOP (12–17 mmHg) in a week. However, intravitreal injection of AMMSC-ERCM or AMESC-ERCM (3.9–4.5 × 10<sup>8</sup> exosomes in 10 μL/eye) markedly recovered the IOP to normal level in 2 weeks, similar to the effect achieved with platelet-derived growth factor-AB (PDGF-AB, 1.5 μg), a reference material. In addition, AMMSC-ERCM, AMESC-ERCM, and PDGF-AB significantly reversed the shrinkage of retinal layers, preserved RGCs, and prevented neural injury in the glaucoma eyes. It was confirmed that stem cell ERCMs containing large numbers of functional molecules such as GFs and NFs improved glaucoma by protecting retinal cells against oxidative and hypoxic injuries in vitro and by recovering IOP and retinal degeneration in vivo. Therefore, it is suggested that stem cell ERCMs could be a promising candidate for the therapy of glaucoma. |
| first_indexed | 2024-03-11T04:17:12Z |
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| issn | 1661-6596 1422-0067 |
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| last_indexed | 2024-03-11T04:17:12Z |
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| spelling | doaj.art-83fa79cde002445cafd974bfcef274302023-11-17T23:04:31ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-04-01249807310.3390/ijms24098073Intraocular Pressure-Lowering and Retina-Protective Effects of Exosome-Rich Conditioned Media from Human Amniotic Membrane Stem Cells in a Rat Model of GlaucomaHye-Rim Seong0Chan Ho Noh1Sangryong Park2Sumin Cho3Seok-Jin Hong4Ah-young Lee5Dongho Geum6Soon-Cheol Hong7Dongsun Park8Tae Myoung Kim9Ehn-Kyoung Choi10Yun-Bae Kim11College of Veterinary Medicine, Chungbuk National University, Cheongju 28644, Republic of KoreaCollege of Veterinary Medicine, Chungbuk National University, Cheongju 28644, Republic of KoreaCentral Research Institute, Designed Cells Co., Ltd., Cheongju 28576, Republic of KoreaCollege of Veterinary Medicine, Chungbuk National University, Cheongju 28644, Republic of KoreaCentral Research Institute, Designed Cells Co., Ltd., Cheongju 28576, Republic of KoreaCentral Research Institute, Designed Cells Co., Ltd., Cheongju 28576, Republic of KoreaDepartment of Biomedical Science, Korea University College of Medicine, Seoul 02841, Republic of KoreaDepartment of Obstetrics and Gynecology, Korea University College of Medicine, Seoul 02841, Republic of KoreaDepartment of Biology Education, Korea National University of Education, Cheongju 28173, Republic of KoreaCentral Research Institute, Designed Cells Co., Ltd., Cheongju 28576, Republic of KoreaCentral Research Institute, Designed Cells Co., Ltd., Cheongju 28576, Republic of KoreaCollege of Veterinary Medicine, Chungbuk National University, Cheongju 28644, Republic of KoreaGlaucoma is one of the most devastating eye diseases, since the disease can develop into blindness and no effective therapeutics are available. Although the exact mechanisms and causes of glaucoma are unknown, increased intraocular pressure (IOP) has been demonstrated to be an important risk factor. Exosomes are lipid nanoparticles secreted from functional cells, including stem cells, and have been found to contain diverse functional molecules that control body function, inhibit inflammation, protect and regenerate cells, and restore damaged tissues. In the present study, exosome-rich conditioned media (ERCMs) were attained via hypoxic culture (2% O<sub>2</sub>) of human amniotic membrane mesenchymal stem cells (AMMSCs) and amniotic membrane epithelial stem cells (AMESCs) containing 50 times more exosome particles than normoxic culture (20% O<sub>2</sub>) medium (NCM). The exosome particles in ERCM were confirmed to be 77 nm in mean size and contain much greater amounts of growth factors (GFs) and neurotrophic factors (NFs) than those in NCM. The glaucoma-therapeutic effects of ERCMs were assessed in retinal cells and a hypertonic (1.8 M) saline-induced high-IOP animal model. CM-DiI-labeled AMMSC exosomes were found to readily penetrate the normal and H<sub>2</sub>O<sub>2</sub>-damaged retinal ganglion cells (RGCs), and AMMSC-ERCM not only facilitated retinal pigment epithelial cell (RPEC) proliferation but also protected against H<sub>2</sub>O<sub>2</sub>- and hypoxia-induced RPEC insults. The IOP of rats challenged with 1.8 M saline increased twice the normal IOP (12–17 mmHg) in a week. However, intravitreal injection of AMMSC-ERCM or AMESC-ERCM (3.9–4.5 × 10<sup>8</sup> exosomes in 10 μL/eye) markedly recovered the IOP to normal level in 2 weeks, similar to the effect achieved with platelet-derived growth factor-AB (PDGF-AB, 1.5 μg), a reference material. In addition, AMMSC-ERCM, AMESC-ERCM, and PDGF-AB significantly reversed the shrinkage of retinal layers, preserved RGCs, and prevented neural injury in the glaucoma eyes. It was confirmed that stem cell ERCMs containing large numbers of functional molecules such as GFs and NFs improved glaucoma by protecting retinal cells against oxidative and hypoxic injuries in vitro and by recovering IOP and retinal degeneration in vivo. Therefore, it is suggested that stem cell ERCMs could be a promising candidate for the therapy of glaucoma.https://www.mdpi.com/1422-0067/24/9/8073glaucomahuman amniotic membrane stem cellexosome-rich conditioned mediumintraocular pressureretinal cell protection |
| spellingShingle | Hye-Rim Seong Chan Ho Noh Sangryong Park Sumin Cho Seok-Jin Hong Ah-young Lee Dongho Geum Soon-Cheol Hong Dongsun Park Tae Myoung Kim Ehn-Kyoung Choi Yun-Bae Kim Intraocular Pressure-Lowering and Retina-Protective Effects of Exosome-Rich Conditioned Media from Human Amniotic Membrane Stem Cells in a Rat Model of Glaucoma International Journal of Molecular Sciences glaucoma human amniotic membrane stem cell exosome-rich conditioned medium intraocular pressure retinal cell protection |
| title | Intraocular Pressure-Lowering and Retina-Protective Effects of Exosome-Rich Conditioned Media from Human Amniotic Membrane Stem Cells in a Rat Model of Glaucoma |
| title_full | Intraocular Pressure-Lowering and Retina-Protective Effects of Exosome-Rich Conditioned Media from Human Amniotic Membrane Stem Cells in a Rat Model of Glaucoma |
| title_fullStr | Intraocular Pressure-Lowering and Retina-Protective Effects of Exosome-Rich Conditioned Media from Human Amniotic Membrane Stem Cells in a Rat Model of Glaucoma |
| title_full_unstemmed | Intraocular Pressure-Lowering and Retina-Protective Effects of Exosome-Rich Conditioned Media from Human Amniotic Membrane Stem Cells in a Rat Model of Glaucoma |
| title_short | Intraocular Pressure-Lowering and Retina-Protective Effects of Exosome-Rich Conditioned Media from Human Amniotic Membrane Stem Cells in a Rat Model of Glaucoma |
| title_sort | intraocular pressure lowering and retina protective effects of exosome rich conditioned media from human amniotic membrane stem cells in a rat model of glaucoma |
| topic | glaucoma human amniotic membrane stem cell exosome-rich conditioned medium intraocular pressure retinal cell protection |
| url | https://www.mdpi.com/1422-0067/24/9/8073 |
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