TY - JOUR
T1 - Intraocular Injection of HyStem Hydrogel Is Tolerated Well in the Rabbit Eye
AU - Glickman, Randolph D.
AU - Onorato, Michael
AU - Campos, Maria M.
AU - O'Boyle, Michael P.
AU - Singh, Ratnesh K.
AU - Zarembinski, Thomas I.
AU - Binette, Francois
AU - Nasonkin, Igor O.
N1 - Funding Information:
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.
Funding Information:
This research was supported by a contract with Lineage Cell Therapeutics, Inc. (formerly BioTime, Inc.).
Publisher Copyright:
© 2021, Mary Ann Liebert, Inc., publishers.
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/1/1
Y1 - 2021/1/1
N2 - Purpose: To determine the long-term biocompatibility of HyStem® hydrogel in the rabbit eye for use as a carrier for cell or drug delivery into the ocular space. Methods: HyStem hydrogel formulation solidifies ∼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 μL/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 μL 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.
AB - Purpose: To determine the long-term biocompatibility of HyStem® hydrogel in the rabbit eye for use as a carrier for cell or drug delivery into the ocular space. Methods: HyStem hydrogel formulation solidifies ∼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 μL/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 μL 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.
KW - HyStem
KW - OCT
KW - electroretinography
KW - hydrogel
KW - intraocular injection
KW - toxicity
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U2 - 10.1089/jop.2020.0042
DO - 10.1089/jop.2020.0042
M3 - Article
C2 - 33449859
AN - SCOPUS:85099723253
VL - 37
SP - 60
EP - 71
JO - Journal of Ocular Pharmacology and Therapeutics
JF - Journal of Ocular Pharmacology and Therapeutics
SN - 1080-7683
IS - 1
ER -