@article{crabtree_uribe_smith_roberts_salmon_bower_song_bastola_hirsch_gilger_2022, title={Inhibition of experimental autoimmune uveitis by intravitreal AAV-Equine-IL10 gene therapy}, volume={17}, ISSN={["1932-6203"]}, url={https://doi.org/10.1371/journal.pone.0270972}, DOI={10.1371/journal.pone.0270972}, abstractNote={Equine recurrent uveitis (ERU) is a spontaneous, painful, and vision threatening disease affecting up to 25% of equine populations worldwide. Current treatments of ERU are non-specific and have many side effects which limits them to short-term use. In order to develop an effective therapy for ERU, we investigated the use of adeno-associated virus (AAV) gene therapy, exploiting a natural immune tolerance mechanism induced by equine interleukin-10 (Equine-IL10). The purpose of this study was to evaluate the therapeutic efficacy of a single intravitreal (IVT) dose of AAV8-Equine-IL10 gene therapy for inhibition of experimental autoimmune uveitis (EAU) in rats. Each rat was dosed intravitreally (IVT) in both eyes with either balanced salt solution (BSS) (control; n = 4), AAV8-Equine-IL10 at a low dose (2.4x109vg; n = 5) or high dose (2.4x1010vg; n = 5). EAU was induced in all groups of rats 7 days after IVT injections and euthanized 21 days post-injection. Ophthalmic examination and aqueous humor (AH) cell counts were recorded with the observer blinded to the treatment groups. Histopathology and qPCR were performed on selected ocular tissues. Data presented herein demonstrate that AAV8-Equine-IL10 treated rats exhibited a significant decrease in clinical inflammatory scores and AH cell counts compared to BSS-treated EAU eyes on days 10, 12 and 14 post EAU induction at both administered vector doses. Mean cellular histologic infiltrative scores were also significantly less in AAV8-Equine-IL10 dosed rats compared to the BSS group. Intravitreal injection of AAV8-Equine-IL10 resulted in Equine-IL10 cDNA expression in the ciliary body, retina, cornea, and optic nerve in a dose-dependent manner. A single IVT injection of AAV8-Equine-IL10 appeared to be well-tolerated and inhibited EAU even at the lowest administered dose. These results demonstrate safety and efficacy of AAV8-Equine-IL10 to prevent EAU and support continued exploration of AAV gene therapy for the treatment of equine and perhaps human recurrent uveitis.}, number={8}, journal={PLOS ONE}, author={Crabtree, Elizabeth and Uribe, Katy and Smith, Sara M. and Roberts, Darby and Salmon, Jacklyn H. and Bower, Jacquelyn J. and Song, Liujiang and Bastola, Prabhakar and Hirsch, Matthew L. and Gilger, Brian C.}, editor={Taylor, Andrew W.Editor}, year={2022}, month={Aug} }
 @article{smith_salmon_abbaraju_amin_gilger_2021, title={Tolerability, pharmacokinetics, and pharmacodynamics of a brinzolamide episcleral sustained release implant in normotensive New Zealand white rabbits}, volume={61}, ISSN={1773-2247}, url={http://dx.doi.org/10.1016/j.jddst.2020.102123}, DOI={10.1016/j.jddst.2020.102123}, abstractNote={Although episcleral drug delivery is a practical and minimally invasive method for sustained release ocular therapeutics, many polymer drug delivery systems induce ocular inflammation and have variable duration of drug release limiting their clinical use. The purpose of this study was to evaluate the in vitro release, tolerability, ocular drug distribution, and pharmacodynamics of brinzolamide released from episcleral silicone matrix devices. In vitro release of low-dose (12 mm × 2 mm; 7.5 mg total drug) and high-dose (20 mm × 2 mm; 12 mg total drug) silicone matrix implants (30% brinzolamide by weight) for 63 days was measured by high-performance liquid chromatography. New Zealand White (NZW) rabbits had either a blank silicone implant (n = 2 eyes), or a low or high-dose brinzolamide implant placed episclerally (n = 8 eyes each). Ocular inflammatory scoring and intraocular pressure (IOP) was measured at 0, 1–7, 10, 14, 21, and 28 days after implantation. Tissues were collected at either day 7 or 28 post implantation for histopathology and aqueous and vitreous humor drug analysis. In vitro release of brinzolamide revealed an initial burst of drug followed by a steady sustained release, with an estimated >12-month release profile. Both high and low-dose implants were well tolerated in NZW rabbits with minimal conjunctival hyperemia that resolved day 21. Eyes with brinzolamide implants had approximately 15–20% sustained reduction of IOP through day 28 after implantation compared to placebo implant eyes. Histopathology revealed mild focal mononuclear cellular infiltrates and fibrosis around the implant site at day 7 and day 28, but no evidence of intraocular toxicity. Brinzolamide was detected in the vitreous humor in a dose and time dependent manner. Episcleral brinzolamide-loaded silicone-matrix implants were extremely well tolerated and delivered sustained drug levels and therapeutic effect for up to 28 days in a rabbit model with an estimated duration of delivery of greater than 12 months.}, journal={Journal of Drug Delivery Science and Technology}, publisher={Elsevier BV}, author={Smith, Sara M. and Salmon, Jacklyn H. and Abbaraju, Santhi and Amin, Rasid and Gilger, Brian C.}, year={2021}, month={Feb}, pages={102123} }
 @article{hirsch_conatser_smith_salmon_wu_buglak_davis_gilger_2017, title={AAV vector-meditated expression of HLA-G reduces injury-induced corneal vascularization, immune cell infiltration, and fibrosis}, volume={7}, ISSN={2045-2322}, url={http://dx.doi.org/10.1038/s41598-017-18002-9}, DOI={10.1038/s41598-017-18002-9}, abstractNote={Abstract}, number={1}, journal={Scientific Reports}, publisher={Springer Nature}, author={Hirsch, Matthew L. and Conatser, Laura M. and Smith, Sara M. and Salmon, Jacklyn H. and Wu, Jerry and Buglak, Nicholas E. and Davis, Rich and Gilger, Brian C.}, year={2017}, month={Dec} }
 @article{smith_westermeyer_mariani_gilger_davidson_2017, title={Optic neuritis in dogs: 96 cases (1983-2016)}, volume={21}, ISSN={1463-5216}, url={http://dx.doi.org/10.1111/vop.12528}, DOI={10.1111/vop.12528}, abstractNote={Abstract}, number={5}, journal={Veterinary Ophthalmology}, publisher={Wiley}, author={Smith, Sara M. and Westermeyer, Hans D. and Mariani, Christopher L. and Gilger, Brian C. and Davidson, Michael G.}, year={2017}, month={Dec}, pages={442–451} }