Visual Function and Retinal Structure with Ganglion Cell Ablation and in Myopia

Purpose: The guinea pig is a model of human retinal physiology and pathology. However, detailed understanding of retinal structure and function is lacking. Here we describe retinal structure and function in healthy guinea pigs, and develop a model of ganglion cell loss. Using imaging analysis techniques developed in these studies, we then evaluated ocular parameters in school age children as a function of age, axial length, and refraction. Methods: 1) In guinea pigs, spatial frequency discrimination was evaluated using optomotor responses. Retinal function was assessed using flash and pattern electroretinogram (ERG). Structure was assessed in vivo using spectral domain optical coherence tomography (SD-OCT. Retrograde retinal ganglion cell degeneration was induced with unilateral optic nerve crush, and changes in retinal structure and visual function were examined. Retinal ganglion cell density and distribution were quantified histologically. 2) In school age children (n = 53), the optic nerve head, lamina cribrosa, retina, and choroid were evaluated using SD-OCT. Images were analyzed in MATLAB and assessed in relation to age, axial length, and refractive error.
Results: 1) Mean spatial frequency discrimination of guinea pigs was 1.65 cycles/degree. The photopic negative response (PhNR) and the oscillatory potentials (OPs) were similar to those in primates. The visual streak was localized the superior retina, with peak ganglion cell density of 1621±129 cells/mm2. With unilateral optic nerve crush, loss of optomotor responses, thinning of retinal nerve fiber layer, and reduction of PhNR and OP1 amplitudes were observed. Pattern ERG responses were largely unaffected. 2) In children, minimum foveal thickness and retinal thickness increased with age. Bruch’s membrane opening area increased with myopic refractive error, and vertical cup-to-disc ratio decreased with increasing axial length and myopic refractive error.
Conclusion: We demonstrated that retinal ganglion cells contribute to the PhNR and OPs of flash ERG in guinea pigs. These findings will be valuable when assessing progression of ocular disease in this animal model. In school age children, we described normative values for retinal and optic nerve head parameters, and demonstrate that ocular remodeling occurs in school age children with normal eye growth and during early stages of myopia.