Casey Eye Institute

Ryals Lab

The Ryals lab develops and evaluates novel therapeutics for inherited retinal degenerations in small animal models. We maintain a colony of many different mouse and rat models of inherited retinal degeneration. Working with these animals, we employ gene-based, cell-based and neuroprotective therapies to slow or mitigate disease progression.

Renee Ryals, Ph.D., was born and raised in Daytona Beach, Florida. She received her BS in Chemistry and her PhD in Molecular Cell Biology and Clinical and Translational Science at the University of Florida. Her dissertation focused on expanding the utility of AAV gene therapy for inherited retinal dystrophies by generating dual AAV vectors for the delivery of large transgenes. After graduation, Renee moved to Portland, Oregon for her post-doctoral training with Dr. Mark Pennesi where she evaluated neuroprotective agents and their ability to slow retinal degeneration in a light-induced retinopathy model. Currently, Renee is an Assistant Professor in the Department of Ophthalmology working alongside both Dr. Pennesi and Dr. Sahay in a combined effort to develop lipid nanoparticle gene therapies for retinal degeneration. In her free time, Dr. Ryals enjoys community and personal development. She enjoys finding opportunities to utilize her process-oriented facilitation and conflict resolution skills.

Dr. Ryals is also affiliated with the Molecular & Medical Genetics department at OHSU. She has collaborations with Dr. Hiroyuki Nakai, Dr. Melanie Gillingham and Dr. Susan Hayflick. Dr. Ryals is also affiliated with the Department of Neuroscience, Oregon National Primate Research Center. She is collaborating with Dr. Martha Neuringer and leading studies that evaluate lipid nanoparticles in the nonhuman primate retina.

Selected projects

Gene therapy

We are developing lipid nanoparticles that efficienctly transfect the retina, especially photoreceptors and RPE. Our aim is to develop LNP mediated gene editing platforms for inherited retinal degenerations.   

Info graphic explaining gene therapy research in the Ryals Lab.

Cell therapy

We are working with multiple companies to evaluate the efficacy of transplanted cells (RPE, photoreceptors, neuroprogenitors) to slow degeneration in the Royal College of Surgeons rats. These studies aid in the IND application process and bring novel therapeutics one step closer to the clinic.

Neuroprotection

We found that a ketogenic & low protein (KLP) diet slows retinal degeneration in the rd10 mouse model of Retinitis Pigmentosa. Additional studies are underway to determine the cellular mechanisms responsible for the neuroprotection.

Image of neuroprotection research being done in the Ryals lab.

Laboratory members

Katie Chirco, Ph.D. Katie is a postdoctoral fellow in Dr. Martha Neuringer’s lab, where she studies inherited retinal degenerations using iPSC-derived human and monkey retinal organoids. She has a close collaboration with Dr. Ryals to investigate novel therapies to treat IRDs, including the development of lipid nanoparticle-based delivery. Prior to joining the team at OHSU, Katie received her Ph.D. in Molecular and Cellular Biology from the University of Iowa under Dr. Robert Mullins, followed by a postdoctoral fellowship with Dr. Deepak Lamba at UCSF. In her free time, Katie enjoys gardening, photography, and spending time outdoors.

Allison Curtis Allie is a Research Assistant II in the Ryals laboratory. She graduated from Pacific Lutheran University in Tacoma, WA with a B.S. in Biology. Her expertise in the Ryals lab includes tissue processing, immunohistochemistry, confocal microscopy, and animal colony maintenance. Allie’s hobbies include reading fantasy and mystery novels, hanging out with her dog Presley, and making art.

Sebastian Arrizabalaga Sebastian is a Research Assistant II in the Ryals laboratory. He graduated from Reed College in Portland, OR, with a B.A. in Chemistry. His expertise include tissue processing, immunohistochemistry, confocal microscopy, and animal colony maintenance. Sebastian’s hobbies include tabletop gaming, 3d printing, and cooking.

Alyse Sheffield - Volunteer

Selected publications

Herrera-Barrera M., Ryals RC., Gautam M., Jozic A., Landry M., Korzun T., Gupta M., Acosta C., Stoddard J., Reynaga R., Tschetter W., Jacomino N., Taratula O., Sun C., Lauer AK., Neuringer M., Sahay G. Peptide-guided lipid nanoparticles deliver mRNA to the neural retina of rodents and nonhuman primates2023, Science Advances, eadd4623, doi:10.1126/sciadv.add4623

Chirco KR, Chew S, Moore AT, Duncan JL, Lamba DA. Allele-specific gene editing to rescue dominant CRX-associated LCA7 phenotypes in a retinal organoid model. Stem Cell Reports. 2021 Nov 9;16(11):2690-2702. doi: 10.1016/j.stemcr.2021.09.007. Epub 2021 Oct 14.PMID: 34653402 

Ryals RC, Patel S, Acosta C, McKinney M, Pennesi ME, Sahay G. The effects of PEGylation on LNP based mRNA delivery to the eye. PLoS One. 2020;15(10):e0241006. doi: 10.1371/journal.pone.0241006. eCollection 2020. PubMed PMID: 33119640; PubMed Central PMCID: PMC7595320.

Ryals RC, Huang SJ, Wafai D, Bernert C, Steele W, Six M, Bonthala S, Titus H, Yang P, Gillingham M, Pennesi ME. A Ketogenic & Low-Protein Diet Slows Retinal Degeneration in rd10 Mice. Transl Vis Sci Technol. 2020 Oct;9(11):18. doi: 10.1167/tvst.9.11.18. eCollection 2020 Oct. PubMed PMID: 33117609; PubMed Central PMCID: PMC7571290.

Patel S, Ryals RC, Weller KK, Pennesi ME, Sahay G. Lipid nanoparticles for delivery of messenger RNA to the back of the eye. J Control Release. 2019 Jun 10;303:91-100. doi: 10.1016/j.jconrel.2019.04.015. Epub 2019 Apr 12. PubMed PMID: 30986436; PubMed Central PMCID: PMC6579630.

Jiang D, Ryals RC, Huang SJ, Weller KK, Titus HE, Robb BM, Saad FW, Salam RA, Hammad H, Yang P, Marks DL, Pennesi ME. Monomethyl Fumarate Protects the Retina From Light-Induced Retinopathy. Invest Ophthalmol Vis Sci. 2019 Mar 1;60(4):1275-1285. doi: 10.1167/iovs.18-24398. PubMed PMID: 30924852; PubMed Central PMCID: PMC6440526.

Ku CA, Ryals RC, Jiang D, Coyner AS, Weller KK, Sinha W, Robb BM, Yang P, Pennesi ME. The Role of ERK1/2 Activation in Sarpogrelate-Mediated Neuroprotection. Invest Ophthalmol Vis Sci. 2018 Jan 1;59(1):462-471. doi: 10.1167/iovs.17-23159. PubMed PMID: 29368005; PubMed Central PMCID: PMC5786286.

Tschetter WW, Govindaiah G, Etherington IM, Guido W, Niell CM.
Refinement of Spatial Receptive Fields in the Developing Mouse Lateral Geniculate Nucleus Is Coordinated with Excitatory and Inhibitory Remodeling. J Neurosci. 2018 May 9;38(19):4531-4542. doi: 10.1523/JNEUROSCI.2857-17.2018. Epub 2018 Apr 16.PMID: 29661964

Ryals RC, Andrews MD, Datta S, Coyner AS, Fischer CM, Wen Y, Pennesi ME, McGill TJ. Long-term Characterization of Retinal Degeneration in Royal College of Surgeons Rats Using Spectral-Domain Optical Coherence Tomography. Invest Ophthalmol Vis Sci. 2017 Mar 1;58(3):1378-1386. doi: 10.1167/iovs.16-20363. PubMed PMID: 28253400; PubMed Central PMCID: PMC5361458.

Coyner AS, Ryals RC, Ku CA, Fischer CM, Patel RC, Datta S, Yang P, Wen Y, Hen R, Pennesi ME. Retinal Neuroprotective Effects of Flibanserin, an FDA-Approved Dual Serotonin Receptor Agonist-Antagonist. PLoS One. 2016;11(7):e0159776. doi: 10.1371/journal.pone.0159776. eCollection 2016. PubMed PMID: 27447833; PubMed Central PMCID: PMC4957778.

Tullis BE, Ryals RC, Coyner AS, Gale MJ, Nicholson A, Ku C, Regis D, Sinha W, Datta S, Wen Y, Yang P, Pennesi ME. Sarpogrelate, a 5-HT2A Receptor Antagonist, Protects the Retina From Light-Induced Retinopathy. Invest Ophthalmol Vis Sci. 2015 Jul;56(8):4560-9. doi: 10.1167/iovs.15-16378. PubMed PMID: 26200496; PubMed Central PMCID: PMC4515947.

Kay CN, Ryals RC, Aslanidi GV, Min SH, Ruan Q, Sun J, Dyka FM, Kasuga D, Ayala AE, Van Vliet K, Agbandje-McKenna M, Hauswirth WW, Boye SL, Boye SE. Targeting photoreceptors via intravitreal delivery using novel, capsid-mutated AAV vectors. PLoS One. 2013;8(4):e62097. doi: 10.1371/journal.pone.0062097. Print 2013. PubMed PMID: 23637972; PubMed Central PMCID: PMC3637363.

Ryals RC, Boye SL, Dinculescu A, Hauswirth WW, Boye SE. Quantifying transduction efficiencies of unmodified and tyrosine capsid mutant AAV vectors in vitro using two ocular cell lines. Mol Vis. 2011 Apr 29;17:1090-102. PubMed PMID: 21552473; PubMed Central PMCID: PMC3087449.