PMID- 33449859 OWN - NLM STAT- MEDLINE DCOM- 20211011 LR - 20220102 IS - 1557-7732 (Electronic) IS - 1080-7683 (Print) IS - 1080-7683 (Linking) VI - 37 IP - 1 DP - 2021 Jan-Feb TI - Intraocular Injection of HyStem Hydrogel Is Tolerated Well in the Rabbit Eye. PG - 60-71 LID - 10.1089/jop.2020.0042 [doi] AB - Purpose: To determine the long-term biocompatibility of HyStem((R)) hydrogel in the rabbit eye for use as a carrier for cell or drug delivery into the ocular space. Methods: HyStem hydrogel formulation solidifies approximately 20 min after reconstitution, thus can potentially form a solid deposit after injection in situ. To study the ocular disposition of fluorescein-labeled HyStem, we delivered 50 muL/eye over 1 min into the vitreous space of the rabbit. We used 3 Dutch-Belted and 3 New Zealand-pigmented rabbits, all females, delivered the gel into the right eyes, and injected 50 muL BSS Plus into the left eyes as a control. Retinal morphology was assessed by optical coherence tomography (OCT) and white light fundus photography. Fluorescence fundus photography enabled measurement of the clearance of the labeled hydrogel from the posterior chamber. Visual function was evaluated using flash and flicker electroretinography (ERG) pre- and postinjection and at weekly intervals thereafter for 6 weeks. Retinal immunohistochemistry for microglial inflammatory markers was carried out with antiglial fibrillary acidic protein (GFAP) antibody, isolectin B4 (IB4), and 4',6-diamidino-2-phenylindole (DAPI). Results: The gel was successfully delivered into the vitreous space without the formation of a discrete retinal deposit. Fundus imaging, OCT measurements of retinal thickness, and immunohistochemical data indicated an absence of retinal inflammation, and ERG indicated no impact on retinal function. The half-time of HyStem clearance calculated from the loss of fundus fluorescence was 3.9 days. Conclusions: HyStem hydrogel appears to be biocompatible in the ocular space of a large eye and safe for long-term intraocular application. FAU - Glickman, Randolph D AU - Glickman RD AD - Department of Ophthalmology, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA. FAU - Onorato, Michael AU - Onorato M AD - Lineage Cell Therapeutics, Inc., Alameda, California, USA. FAU - Campos, Maria M AU - Campos MM AD - Histopathology Core, National Eye Institute, National Institutes of Health, Bethesda, Maryland, USA. FAU - O'Boyle, Michael P AU - O'Boyle MP AD - Research Imaging Institute, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA. FAU - Singh, Ratnesh K AU - Singh RK AD - Lineage Cell Therapeutics, Inc., Alameda, California, USA. FAU - Zarembinski, Thomas I AU - Zarembinski TI AD - Lineage Cell Therapeutics, Inc., Alameda, California, USA. FAU - Binette, Francois AU - Binette F AD - Lineage Cell Therapeutics, Inc., Alameda, California, USA. FAU - Nasonkin, Igor O AU - Nasonkin IO AD - Lineage Cell Therapeutics, Inc., Alameda, California, USA. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Ocul Pharmacol Ther JT - Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics JID - 9511091 RN - 0 (Biocompatible Materials) RN - 0 (Hydrogels) SB - IM MH - Animals MH - Biocompatible Materials/*administration & dosage MH - Drug Tolerance MH - Eye/*drug effects MH - Female MH - Hydrogels/*administration & dosage MH - Injections, Intraocular MH - Rabbits PMC - PMC8020505 OTO - NOTNLM OT - HyStem OT - OCT OT - electroretinography OT - hydrogel OT - intraocular injection OT - toxicity COIS- R.D.G. (contract research project) and M.P.O. received financial support from Lineage Cell Therapeutics, Inc. F.B., I.O.N., M.O., and R.K.S. were employees of Lineage Cell Therapeutics, Inc. EDAT- 2021/01/16 06:00 MHDA- 2021/10/12 06:00 PMCR- 2022/01/01 CRDT- 2021/01/15 17:10 PHST- 2021/01/15 17:10 [entrez] PHST- 2021/01/16 06:00 [pubmed] PHST- 2021/10/12 06:00 [medline] PHST- 2022/01/01 00:00 [pmc-release] AID - 10.1089/jop.2020.0042 [pii] AID - 10.1089/jop.2020.0042 [doi] PST - ppublish SO - J Ocul Pharmacol Ther. 2021 Jan-Feb;37(1):60-71. doi: 10.1089/jop.2020.0042.