Modulatory influence of stimulus parameters on optokinetic head-tracking response

Doheny Retina Institute, Doheny Eye Institute, 1450 San Pablo St., Los Angeles, CA 90033, United States.
Neuroscience Letters (Impact Factor: 2.03). 07/2010; 479(2):92-6. DOI: 10.1016/j.neulet.2010.05.031
Source: PubMed


Optokinetic testing is a non-invasive technique, widely used for visual functional evaluation in rodents. The modulatory influence of optokinetic stimulus parameters such as contrast level and grating speed on head-tracking response in normal and retinal degenerate (RD) mice (rd10) and rats (S334ter-line-3) was evaluated using a computer-based testing apparatus. In normal (non-RD) mice and rats, specific stripe width and grating speed was found to evoke maximum optokinetic head-tracking response. In line-3 RD rats, the contrast sensitivity loss was slow and remained close to the baseline (normal control) level until very late in the disease, whereas, in rd10 mice the progression of the contrast sensitivity loss was more rapid. Observed differences between rd10 mice and line-3 RD rats in the progression of contrast sensitivity loss may not be directly related to the degree of photoreceptor loss. In young RD mice, the modulatory influence of stimulus parameters on optokinetic head-tracking response was similar to normal control animals. During later stages, slower grating speed was required to evoke the maximum optokinetic response. Grating speed had lesser apparent influence on the response properties of line-3 RD rats. Discrepancies between the two RD models in the modulatory influence of optokinetic stimulus parameters can be the manifestation of fundamental species differences and/or differences in the degeneration pattern. This study highlights the importance of careful selection of appropriate stimulus parameters for testing optokinetic head-tracking response in RD animals.

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    • "Spatial acuity, which in rodents is low due to spatial summation, can be observed after RPE [59] or photoreceptor cell damage [60]. Likewise, loss of contrast sensitivity is a manifestation of photoreceptor cell loss in retinal degenerate mice (rd10) [61] or the Royal College of Surgeons rat [62]. Spatial frequency threshold (spatial acuity) in WT mice after CE did not differ from that of control animals exposed to room air (0.34±0.01 cyc/deg versus 0.37±0.01 "
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    ABSTRACT: Age-related macular degeneration (AMD), a complex disease involving genetic variants and environmental insults, is among the leading causes of blindness in Western populations. Genetic and histologic evidence implicate the complement system in AMD pathogenesis; and smoking is the major environmental risk factor associated with increased disease risk. Although previous studies have demonstrated that cigarette smoke exposure (CE) causes retinal pigment epithelium (RPE) defects in mice, and smoking leads to complement activation in patients, it is unknown whether complement activation is causative in the development of CE pathology; and if so, which complement pathway is required. Mice were exposed to cigarette smoke or clean, filtered air for 6 months. The effects of CE were analyzed in wildtype (WT) mice or mice without a functional complement alternative pathway (AP; CFB(-/-) ) using molecular, histological, electrophysiological, and behavioral outcomes. CE in WT mice exhibited a significant reduction in function of both rods and cones as determined by electroretinography and contrast sensitivity measurements, concomitant with a thinning of the nuclear layers as measured by SD-OCT imaging and histology. Gene expression analyses suggested that alterations in both photoreceptors and RPE/choroid might contribute to the observed loss of function, and visualization of complement C3d deposition implies the RPE/Bruch's membrane (BrM) complex as the target of AP activity. RPE/BrM alterations include an increase in mitochondrial size concomitant with an apical shift in mitochondrial distribution within the RPE and a thickening of BrM. CFB(-/-) mice were protected from developing these CE-mediated alterations. Taken together, these findings provide clear evidence that ocular pathology generated in CE mice is dependent on complement activation and requires the AP. Identifying animal models with RPE/BrM damage and verifying which aspects of pathology are dependent upon complement activation is essential for developing novel complement-based treatment approaches for the treatment of AMD.
    PLoS ONE 06/2013; 8(6):e67894. DOI:10.1371/journal.pone.0067894 · 3.23 Impact Factor
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    • "Notably, retinal thickening (consistent with DME) has been detected in a small number of available models such as monkeys. Vision loss or impairment is also now being studied in mice and rats using the optokinetic response (Thomas et al., 2010); investigating the cause of a diabetes-induced reduction in visual function might provide new insight into the causes of vision loss in diabetic humans. "
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