Date of Award
Spring 2008
Document Type
Dissertation - Restricted
Degree Name
Doctor of Philosophy (PhD)
Department
Biomedical Engineering
First Advisor
Neitz, Jay
Second Advisor
Carroll, Joseph
Third Advisor
Clough, Anne
Abstract
Recently, gene therapy has shown potential in treating color blindness through the insertion of new long- (L-) wavelength spectral sensitivity into protanopic monkey and gerbil retinas. The opsin was inserted into an existing subset of the middle- (M-) wavelength sensitive cone photoreceptors via an adeno-associated virus. Knowing the retinal area transfected by the virus in vivo is an important aspect to the project because an important goal is to cover a portion of the fovea. To this end, a new wide-field color LED-based multifocal-electroretinogram (mf-ERG) was developed and validated for specific aim I. The new mf-ERG can isolate responses from L-cones using a 650 nm wavelength light, improves existing mf-ERG technology by measuring over 70 degrees of visual angle (clinical mf-ERGs stimulate over 30 degrees), and maintains viable SNR out in the far periphery. Evidence from messenger RNA data from human cadavers has shown the ratio of L:M cone photopigment increases from fovea to far periphery. This result has been difficult to corroborate in vivo because current imaging techniques cannot gauge cone-photoreceptor type beyond ∼eight degrees. The mf-ERG developed in specific aim I was used in specific aim II to gauge sensitivity of green light versus red light as a function of eccentricity among color-normal individuals. The goal was to corroborate the in vitro result. In the vision community there is a growing body of literature showing high variation in cone photoreceptor mosaics. Despite these differences individuals show no difference in the ability to discriminate colors when tested on a battery of color vision tests. Additionally, the expression of a new spectral photopigment in dichromatic retinas has shown, behaviorally, the animal is immediately able to take advantage of the new photopigment to discriminate colors. Specific aim III encompasses developing a mathematical model that can, using the spectral sensitivities of the S-, M-, and L-cones, extract the six fundamental percepts of whiteness, blackness, greenness, redness, yellowness, and blueness while being constrained by known anatomy and experimental findings listed above. Developing such a model may elucidate underlying circuitry of the retina.