| Title: |
Three-dimensional spheroids of choroid-retinal vascular endothelial cells as an in-vitro model for diabetic retinopathy: Proof-of-concept investigation |
| Authors: |
Manish Gore; Ankit Tiwari; Devashree Jahagirdar; Angayarkanni Narayanasamy; Ratnesh Jain; Prajakta Dandekar |
| Source: |
Current Research in Pharmacology and Drug Discovery, Vol 3, Iss , Pp 100111- (2022) |
| Publisher Information: |
Elsevier, 2022. |
| Publication Year: |
2022 |
| Collection: |
LCC:Therapeutics. Pharmacology |
| Subject Terms: |
Diabetic retinopathy; Three-dimensional; In-vitro; Choroid-retinal vascular endothelial cells; Spheroids; Angiogenesis; Therapeutics. Pharmacology; RM1-950 |
| Description: |
Diabetic retinopathy (DR) is a primary microvascular complication of diabetes mellitus and a vision-threatening condition. Vascular endothelial growth factor (VEGF) induces neovascularization and causes metabolic damage to the retinal and choroidal vasculature in diabetic patients. Existing drug screening models and treatment strategies for DR need to be refined through the establishment of relevant pre-clinical models, which may enable development of effective and safe therapies. The present study discusses the development of an in-vitro three-dimensional (3D) spheroid model, using RF/6A choroid-retinal vascular endothelial cells, to closely mimic the in-vivo disease condition. Compact, reproducibly-sized, viable and proliferating RF/6A spheroids were fabricated, as confirmed by microscopy, live/dead assay, cell proliferation assay and histological staining. In-vitro angiogenesis was studied by evaluating individual effects of VEGF and an anti-VEGF monoclonal antibody, Bevacizumab, and their combination on cellular proliferation and 3D endothelial sprout formation. VEGF stimulated angiogenic sprouting while Bevacizumab demonstrated a dose-dependent anti-angiogenic effect, as determined from the cellular proliferation observed and extent and length of sprouting. These investigations validated the potential of RF/6A spheroids in providing an alternative-to-animal, pathophysiologically-relevant model to facilitate pre-clinical and biomedical research related to DR. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
2590-2571 |
| Relation: |
http://www.sciencedirect.com/science/article/pii/S2590257122000311; https://doaj.org/toc/2590-2571 |
| DOI: |
10.1016/j.crphar.2022.100111 |
| Access URL: |
https://doaj.org/article/1eac74892ec24efea8433fc124f7a4e6 |
| Accession Number: |
edsdoj.1eac74892ec24efea8433fc124f7a4e6 |
| Database: |
Directory of Open Access Journals |