301 E. Muhammad Ali Boulevard, Louisville KY 40202
Telephone: 502-852-3386 (office) 502-852-0162 (lab) Fax: 502-852-3588
B.S. & MS.:
University of Maryland, College Park M.D. – 1974 – 1977
Neurobiology – The University at Albany, Albany, NY – 1983
(1) Visual System Plasticity & Processing (P.D. Spear) Departments of Psychology & Ophthalmology, University of Wisconsin, Madison, WI – 1983-1987
(2) Circuitry Underlying Basic Retinal Signaling (L.R. Stanford) Waisman Center, University of Wisconsin, Madison, WI – 1987-1992
(3) Genetic Manipulation of the Nervous System (A. Messing) School of Veterinary Medicine, University of Wisconsin, Madison, WI – 1992-1993
(1) Assistant/Associate Scientist, Waisman Center on Mental Retardation & Human Development, University of Wisconsin, Madison, WI – 1993-1996
(2) Assistant/Associate/Professor, Department of Psychological & Brain Sciences, University of Louisville, Louisville, KY, 1997 – 2007
(3) Professor, Department of Ophthalmology & Visual Sciences, University of Louisville, Louisville, KY, 2007 – present.
(4) Joint appointments – Departments of : Anatomical Sciences & Neurobiology and Psychological & Brain Sciences.
My research uses electrophysiological techniques to evaluate normal retinal function, dysfunction caused by blinding retinal diseases and the restoration of function using a variety of therapeutic strategies. We can use our understanding or normal retinal function and disease-related changes to construct optimal therapeutic strategies and evaluate how they ameliorate the effects of disease.
Retinitis pigmentosa (RP) is a family of blinding eye diseases caused by photoreceptor degeneration. The absence of the cells that for this primary signal leads to blindness. My interest in RP involves the evaluation of therapies to restore vision: replacing degenerated photoreceptors either with: (1) new stem or other embryonic cells, manipulated to become photoreceptors or (2) prosthetics devices that replace the photoreceptor signal with an electronic signal to light.
Glaucoma is caused by increased intraocular pressure and leads to ganglion cell death, which eliminates the link between the retinal output and central visual processing. We are parsing out of the effects of increased intraocular pressure and aging on ganglion cells.
Congenital Stationary Night Blindness (CSNB) is a family of diseases in which signaling is eliminated between rod photoreceptors and their postsynaptic targets, rod bipolar cells. This deafferents the retinal circuit that is responsible for vision under dim lighting. My interest in CSNB involves understanding the basic interplay between excitation and inhibition in the retinal circuit and its normal development. Because of the targeted nature of this disease, we are hopeful that a gene therapy approach can be developed to restore night vision.
My work utilizes rodent disease models whose mutations mimic those found in human patients. While molecular manipulation of rodents is a fairly common approach, we have recently developed a mutant NIH miniature swine model of a common form of autosomal dominant RP (Pro23His rhodopsin mutation) in collaboration with the National Swine Resource Research Center at University of Missouri. More genetically modified mini-swine models are in the pipeline to examine other retinal diseases.
- Demas, J., Sagdullaev, B.T., Green, E. Jaubert-Miazza, L., McCall, M.A., Gregg, R.G. Wong, R.O.L., Guido, W. Failure to Maintain Eye-Specific Segregation in nob, a Mutant with Abnormally Patterned Retinal Activity. Neuron Apr 20; 50(2): 247-259 (2006).
- Sagdullaev, B.T., McCall, M.A. Lukasiewicz, P.D. Presynaptic inhibition modulates spillover, creating distinct dynamic response ranges of sensory output (Neuron June 15; 50 (6): 1 – 13 (2006).DeMarco, P.J. Yarbrough, G.Y., Yee, C.W., McClean, G.Y., Sagdullaev, B.T., Ball, S.L. & McCall, M.A. Stimulation via a subretinally placed prosthetic elicits central activity and induces a trophic effect on visual responses. Investigative Ophthalmology & Visual Sciences 2007 Feb;48(2):916-26).
- Eggers, E.D., McCall, M.A and Lukasiewicz, P.D. Presynaptic inhibition differentially shapes transmission in distinct retinal circuits J. Physiology (Lond) 2007, Jul 15;582(Pt 2):569-82).
- Gregg, R.G., Kamermans,M., Klooster,J., Lukasiewicz, P.D., Peachey, N.S., Vessey, K.A., McCall, M.A. Nyctalopin Expression in Retinal Bipolar Cells Restores Visual Function in a Mouse Model of Complete X-linked Congenital Stationary Night Blindness. J. Neurophysiol 2007 Nov;98(5):3023-33).
- van Genderen MM, Bijveld MM, Claassen YB, Florijn RJ, Pearring JN, Meire FM, McCall MA, Riemslag FC, Gregg RG, Bergen AA, Kamermans M. Mutations in TRPM1 are a common cause of complete congenital stationary night blindness. Am J Hum Genet. 2009 Nov;85(5):730-6.
- 6. Herrmann R, Heflin SJ, Hammond T, Lee B, Wang J, Gainetdinov RR, Caron MG, Eggers ED, Frishman LJ, McCall MA, Arshavsky VY. Rod Vision Is Controlled by Dopamine-Dependent Sensitization of Rod Bipolar Cells by GABA. Neuron. 2011 Oct 6;72(1):101-10.
- Ross, J.W., Fernandez de Castro, J. Zhao, J., Samuel, M., Walters, E. Rios, C., Bray-Ward, P., Jones, B.W., Marc, R.E., Wang, W., Zhou, L., Noel, J.M., McCall, M.A., DeMarco, P.J., Prather, R.S., Kaplan, H.J. Generation of an inbred miniature pig model of retinitis pigmentosa Investigative Ophthalmology & Visual Science 2012, Jan 31;53(1):501-7.
- Peachey, N.S., Ray, T.A.,Florijn, R.,Rowe, L.B., Spoerdsma, T., Contreras-Alcantara, S., Baba, K., Tosini, G., Pozdeyev, N., Iuvone, P.M., Bojang, Jr., P., Pearring, J.N., Simonsz, H.J., van Genderen, M., Birch, D.G., Traboulsi, E.I., Dorfman, A., Lopez, I., Ren, H., Goldberg, A.F., Nishina, P.M., Lachapelle, P., McCall, M.A., Koenekoop, R.C., Bergen, A.A., Kamermans, M., Gregg, R.G., GPR179 is required for depolarizing bipolar cell function and is mutated in autosomal recessive complete congenital stationary night blindness Am J Hum Genet. 2012, Feb 10;90(2):331-9.
- Nobles, R.D., Zhang, C., McCall, M.A. Selective glycine receptor α2 subunit control of crossover inhibition between the on and off retinal pathways. J. Neuroscience 2012, Mar 7;32(10):3321-32.).
- Fernandez de Castro, JP; Scott, PA; Fransen, JW; Demas, J; DeMarco, P.J; Kaplan, HJ; McCall, MA Cone Photoreceptors Develop Normally in the Absence of Functional Rod Photoreceptors in a Transgenic Swine Model of Retinitis Pigmentosa Investigative Ophthalmology & Visual Sciences 2014 Apr 17;55(4):2460-8.
- Ray, TA; Heath, KM; Hasan, N; Noel, JM, Samuels, IS; Martemyanov, KA; Peachey, NS; McCall, MA; Gregg, RG (co corresponding senior authors) GPR179 is required for high sensitivity of the mGluR6 signaling cascade in depolarizing bipolar cells Journal of Neuroscience, 2014 34(18):6334-43.
- Fransen, JW; Pangeni, G; Pardue, MT; McCall, MA Local signaling from a retinal prosthetic device in a rodent RP model in vivo Journal of Neural Engineering, 2014 Aug;11(4):046012. doi: 10.1088/1741-2560/11/4/046012. Epub 2014 Jun 18.
- Zhang, C; Ramponi, S.; Roska, B.; McCall, MA GlyRα1-mediated Inhibition Improves the Fidelity of the A-Type OFF Retinal Ganglion Cell Response, 2014 J. Neurophysiology, Dec 15;112(12):3125-37. doi: 10.1152/jn.00505.2014. Epub 2014 Sep 17.
- Fransen, JW; Pangeni, G.; Pyle, IS; McCall MA Retinal Responses: Differences Between ON and OFF Pathway Transmission to the Superior Colliculus J Neurophysiol. 2015 Oct;114(4):2368-75. doi: 10.1152/jn.00600.2015. Epub 2015 Aug 5.
- Scalabrino, ML; Sanford L. Boye1, SL; Fransen, KM; Noel, JM, Dyka, FM; Min, SH; Ruan, Q; de Leeuw, CN; Simpson, EM; Gregg, RG; McCall, MA; Peachey, NS; Boye, SE Intravitreal delivery of a novel AAV vector targets ON bipolar cells and restores visual function in a mouse model of complete Congenital Stationary Night Blindness Hum Mol Genet. 2015 Nov 1;24(21):6229-39. doi: 10.1093/hmg/ddv341. Epub 2015 Aug 26.
- Sarria, I, Orlandi, C, McCall, MA, Gregg, RF & Martemyanov K : Intermolecular interaction between anchoring subunits specify subcellular targeting and function of RGS proteins in retina ON-bipolar neurons Journal of Neuroscience, 2016 Mar 9;36(10):2915-25.