摘要
This study explored the novel strategy of hypoxic preconditioning of Bone Marrow Mesenchymal Stem Cells (BM-MSCs) before intra vitreal transplantation to improve neuroprotective effects of Retinal Ganglion Cells (RGCs) in Acute Glaucoma Models. The methods of this research were isolated mesenchymal stem cells from the bone marrow of adult wild-type Sprague-Dawley (SD) rats. BM-MSCs were cultured under normoxic or hypoxic (1% oxygen for 24 hours) conditions. Normoxic or hypoxic BM-MSCs were transplanted intravitreally 1 week after ocular hypertension induction by acutely increasing IOP to 100 - 120 mmHg for 60 minutes. Rats were killed 4 weeks after transplanted. Apoptosis was examined by tunnel assay and expression Brn3b (Brn3b = RGCs marker) by immunohistochemical analysis of the retina. Results showed that transplantation of hypoxic preconditioning BM-MSCs in acute glaucoma models resulted in a significant apoptosis decreasing (p < 0.05) and an significant increasing in RGCs (p < 0.05), as well as enhanced mor-phologic and functional benefits of stem cell therapy versus normoxic BM-MSCs transplantation. Conclusions: Hypoxic preconditioning enhances the capacity of BM-MSCs transplantation to improve neuroprotective effects of RGCs in Acute Glaucoma Models.
This study explored the novel strategy of hypoxic preconditioning of Bone Marrow Mesenchymal Stem Cells (BM-MSCs) before intra vitreal transplantation to improve neuroprotective effects of Retinal Ganglion Cells (RGCs) in Acute Glaucoma Models. The methods of this research were isolated mesenchymal stem cells from the bone marrow of adult wild-type Sprague-Dawley (SD) rats. BM-MSCs were cultured under normoxic or hypoxic (1% oxygen for 24 hours) conditions. Normoxic or hypoxic BM-MSCs were transplanted intravitreally 1 week after ocular hypertension induction by acutely increasing IOP to 100 - 120 mmHg for 60 minutes. Rats were killed 4 weeks after transplanted. Apoptosis was examined by tunnel assay and expression Brn3b (Brn3b = RGCs marker) by immunohistochemical analysis of the retina. Results showed that transplantation of hypoxic preconditioning BM-MSCs in acute glaucoma models resulted in a significant apoptosis decreasing (p < 0.05) and an significant increasing in RGCs (p < 0.05), as well as enhanced mor-phologic and functional benefits of stem cell therapy versus normoxic BM-MSCs transplantation. Conclusions: Hypoxic preconditioning enhances the capacity of BM-MSCs transplantation to improve neuroprotective effects of RGCs in Acute Glaucoma Models.
作者
Titiek Ernawati
Gatut Suhendro
I Ketut Sudiana
Suhartono Taat Putra
Harjanto JM
Sunarjo
Agus Turchan
Fedik Abdul Rantam
Titiek Ernawati;Gatut Suhendro;I Ketut Sudiana;Suhartono Taat Putra;Harjanto JM; ;Sunarjo;Agus Turchan;Fedik Abdul Rantam(Department of Ophthalmology, School of Medicine, Widya Mandala University, Surabaya, Indonesia;PHC Hospital, Surabaya, Indonesia;Department of Ophthalmology, School of Medicine, Airlangga University, Surabaya, Indonesia;Dr. Soetomo General Hospital, Surabaya, Indonesia;Department of Pathology Anatomy, School of Medicine, Airlangga University, Surabaya, Indonesia;Department of Physiology, School of Medicine, Airlangga University, Surabaya, Indonesia;Department of Public Health, School of Medicine, Airlangga University, Surabaya, Indonesia;Department of NeuroSurgery, School of Medicine, Airlangga University, Surabaya, Indonesia;Laboratory of Stem Cell, Institute of Tropical Disease, Airlangga University, Surabaya, Indonesia;Regenerative Medicine & Stem Cell Centre, Airlangga University, Surabaya, Indonesia;Laboratory of Virology and Immunology, Department of Microbiology, School of Veterinary Medicine, Airlangga University, Surabaya, Indonesia)