Nanoscale Modulators of Retinal Postsynaptic Receptors

David Pepperberg, PhD
Board of Trustees of the (Chicago, IL)
Year Awarded:
2006
Grant Duration:
April 1, 2006 to March 31, 2008
Disease:
Macular Degeneration
Award Amount:
$100,000
Grant Reference ID:
M2006016
Award Type:
Standard
Award Region:
US Midwestern

Co-principal Investigators

Haohua Qian, PhD
Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago

Nanoscale Modulators of Retinal Postsynaptic Receptors

Details

In the normally functioning retina, visual signals initiated in the rod and cone photoreceptor cells are transmitted to other nerve cells of the retina called “post-photoreceptor” cells. Patients with retinal degenerative diseases such as age-related macular degeneration (AMD) have deteriorating rods and cones. However, there is reason to believe that in certain patients, post-photoreceptor retinal nerve cells remain capable of functioning.

Functional post-photoreceptor cells suggest an opportunity to restore sight in AMD patients. Our idea is to develop molecular structures (tiny machines) that would interact with specific proteins on the surfaces of these cells and stimulate them in response to light that enters the eye. The molecular structures that we envision, once introduced into the patient's diseases retina, would bind tightly to the post-photoreceptor cells and initiate visual signals, thereby bypassing the deteriorated rod and cone cells. The overall goal of the project is to design and construct structures that can achieve this challenging objective in molecular bioengineering and nanotechnology. These molecular machines could serve as a therapy for AMD, and additionally could provide a model for treating other neurodegenerative diseases.

Publications

Chowdhury, S., Muni, N.J., Greenwood, N.P., Pepperberg, D.R. and Standaert, R.F. (2007) Phosphonic acid analogs of GABA through reductive dealkylation of phosphonic diesters with lithium trialkylborohydrides. Bioorg Med Chem Lett. 17(13):3745-8. Epub 2007 Apr 10. PubMed Icon Google Scholar Icon

Gussin, H.A., Tomlinson, I.D., Little, D.M., Qian, H., Rosenthal, S.J. and Pepperberg, D.R. (2006) Binding of muscimol-conjugated quantum dots to GABAc receptors. J. Amer. Chem. Soc. 128(49):15701-15713. PubMed Icon Google Scholar Icon

Kang Derwent JJ, Saszik SM, Maeda H, Little DM, Pardue MT, Frishman LJ & Pepperberg DR (2007) Test of the paired-flash electroretinographic method in mice lacking b-waves. Visual Neurosci. 24:141-149. PubMed Icon Google Scholar Icon

Qtaishat NM & Pepperberg DR (2007) Preservation of retinoid influx into eye tissues of ABCR-deficient mice. Current Eye Res. 32:1073-1082. PubMed Icon Google Scholar Icon

Tomlinson ID, Gussin HA, Little DM, Warnement, MR, Qian H, Pepperberg DR & Rosenthal SJ (2007) Imaging GABAC receptors with ligand-conjugated quantum dots. J. Biomed. Biotechnol. 2007, Article ID 76514; doi:10.1155/2007/76514. PubMed Icon Google Scholar Icon

Pawar AS, Qtaishat NM, Little DM & Pepperberg DR (2008) Recovery of rod photoresponses in ABCR-deficient mice. Invest. Ophthalmol. Vis. Sci. 49:2743- 2755. PubMed Icon Google Scholar Icon

Yue L, Pawlowski M, Dellal SS, Xie A, Feng F, Otis TS, Bruzik KS, Qian H, Pepperberg DR. Robust photoregulation of GABA(A) receptors by allosteric modulation with a propofol analogue. Nat Commun. 2012 Oct 2;3:1095. doi: 10.1038/ncomms2094. PubMed Icon Google Scholar Icon