Optomotor and immunohistochemical changes in the juvenile S334ter rat

Abstract

The aim of this study was to examine the temporal relationship between behaviorally measured visual thresholds, photoreceptor degeneration and dysfunction, synaptic and neuronal morphology changes in the retina in the S334ter line 4 rat. Specifically, we examined the optokinetic tracking (OKT) behavior in S334ter rats daily and found that OKT thresholds reflected normal values at eye-opening but quickly reduced to a non-response level by postnatal day (P) 22. By contrast, the scotopic electroretinogram (ERG) showed a much slower degeneration, with substantial scotopic function remaining after P90 as previously demonstrated for this line of rats. Photopic b-wave amplitudes revealed functional levels between 70 and 100% of normal between P30 and P90. Histological evidence demonstrated that photoreceptor degeneration occurred over many months, with an outer nuclear layer (ONL) roughly half the thickness of a normal age-matched control at P90. Immunohistochemical analysis revealed a number of changes in retinal morphology in the Tg S334ter line 4 rat that occur at or before P40 including: elevated levels of rod opsin expression in the ONL, cone photoreceptor morphology changes, glial cell activation, inner retinal neuron sprouting, and microglial cell activation. Many of these changes were evident at P30 and in some cases as early as eye opening (P15). Thus, the morphological changes occurred in concert with or before the very rapid loss of the behavioral (OKT) responses, and significantly before the loss of photoreceptors and photoreceptor function.

Psychophysical testing in rodent models of glaucomatous optic neuropathy

“…Direction-selective retinal ganglion cells (DS-RGCs) detect the motion of the stimuli in a preferred direction (Ackert et al, 2009; Giolli et al, 2006; Spoida et al, 2012; Stahl, 2004; van Alphen et al, 2010; Yonehara et al, 2009). The optomotor response (OMR) is used in behavioral tests to measure the ability of an animal to distinguish spatial frequency, the number of pattern repetitions over a given distance, and contrast sensitivity, the ability to distinguish individual parts of a visual image (Burroughs et al, 2011; Douglas et al, 2005; Kaja et al, 2014; Kandel et al, 2000; McGill et al, 2012b; Prusky et al, 2004). Behavioral tests measuring an animal’s ability to resolve the spatial frequency and contrast of visual stimuli are employed to identify changes in visual acuity and contrast sensitivity thresholds, respectively, as critical first changes in glaucoma disease development (Burroughs et al, 2011; Kaja et al, 2011; Kaja et al, 2014).…”

A system to measure the pupil response to steady lights in freely behaving mice

“…These studies compare structure-function changes at the cellular and retinal levels by combining traditional approaches such as immunohistochemistry, electrophysiology and biochemistry (Huberman and Niell, 2011; Pinto and Enroth-Cugell, 2000). More recently, these traditional approaches have been complemented with psychophysical tests that assess the limits of vision in mouse (Busse et al, 2011; Histed et al, 2012; Naarendorp et al, 2010; Prusky et al, 2004) and can track visual changes in models of retinal degeneration (McGill et al, 2012; Umino et al, 2006), retinal transplantation (Pearson et al, 2012) and gene therapy treatment (Boye et al, 2013; Pang et al, 2011). A primary objective of these visual psychophysical assays is to determine the minimal amount of light or contrast that is necessary to elicit a visual response in animals (also known as visual threshold) (Stebbins, 1970).…”

Defining the Relationships Among Retinal Function, Layer Thickness and Visual Behavior During Oxidative Stress-Induced Retinal Degeneration

“…8, 9, 10 The OKT assay is a well-characterized technique that is used to detect the level of visual acuity in many vertebrates organisms, including mice and humans. 8, 11, 12, 13, 14 However, the extent that visual behavior decline correlates with changes in retinal structure and function is still not clear.…”