Qun Guo

A potential spontaneous rat model of X-linked congenital stationary night blindness

Purpose: To describe a possible spontaneous rat model of X-linked congenital stationary night blindness (CSNB). Methods: Experimental animals were generated by mating the affected animal to normal rats, and from interbreeding littermates. To define the inheritance pattern, full-field electroretinograms (ERGs) were recorded from all progeny. Results: During the course of other experiments, an affected male rat was identified by a reduced amplitude ERG b-wave. When this rat was mated to normal Sprague–Dawley rats, all of the F1 progeny had normal ERG waveforms. When F1 offspring were interbred, 51% of the male offspring had b-wave reductions while all female offspring had normal ERG waveforms. When F1 females were backcrossed to the original affected male, b-wave reductions were noted in both male and female offspring; overall, 46.8% of the backcross progeny exhibited a b-wave reduction. In affected animals, the b-wave was selectively affected as the a-wave appeared to retain normal amplitude and kinetics at 1–4 months old. Cone ERGs were significantly reduced in amplitude and somewhat delayed. Similar ERG results were also obtained under the same stimulus conditions from human patients with complete CSNB (CSNB1). Conclusions: The inheritance pattern is consistent with an X-linked recessive trait. The electrophysiological results suggest that this mutant rat line may provide another model for CSNB1.

A novel middle-wavelength opsin (M-opsin) null-mutation in the retinal cone dysfunction rat

The disease-causing gene which underlies a naturally occurring X-linked mutant cone dysfunction Sprague-Dawley rat model was investigated. Full-field electroretinogram (ERG) and simple sequence length polymorphism analyses were applied to 441-second filial generation rats that were derived from crossing a mutant rat and a Brown-Norway rat. After identifying a mutation mapping within the telomeric region of chromosome X, a candidate gene related to retinal cone function in this region was further screened using real-time PCR, immunohistochemistry and histological methods. The results showed that a G-to-T substitution at the splice acceptor site of intron 4 was present in the opsin 1, medium-wave sensitive (Opn1mw) gene, thereby causing down-regulated transcription and translation. These changes were consistent with abnormities seen in the ERG response. However, there was no significant histological change in the mutant rat retina. Therefore, we infer from this that the causative gene for the mutation is Opn1mw and consequently term this a middle-wavelength opsin cone dysfunction (MCD) rat model. The deficiency in vision of the MCD rat is similar to the color vision defects that occur in humans with a color vision defect but without recessive retinal degeneration. This rat model may be useful for understanding the mechanism that is responsible for color vision and for developing clinical therapies for several retinal dystrophies caused by cone opsin deficiencies.

Intraocular pressure and ocular perfusion pressure in myopes during 21 min head-down rest.

INTRODUCTION Myopic eyes show structural differences from normal eyes and may respond differently to microgravity, increasing the risk for possible development of ocular hypertension and glaucoma on orbit. In this experiment we used head-down rest (HDR) at an angle of 15 degrees to produce hydrostatic changes similar to acute exposure to microgravity. METHODS There were 65 subjects (129 eyes) who were divided into groups characterized by refraction: emmetropes (N = 46; refraction error between -0.99 D and +0.10 D), low myopes (N = 39; > or = -1.0 D to < -3.0 D), and moderate myopes (N = 44; > or = -3.0 D to < -6.0 D). Each subject was studied resting in a horizontal position and after 1, 6, 11, 16, and 21 min of HDR. Measured variables included systolic and diastolic blood pressure (SBP and DBP, respectively), intraocular pressure (IOP), and ocular perfusion pressure (OPP). RESULTS The mean values of IOP increased significantly in all eyes during HDR, with IOP peaking at 6 min. Compared to emmetropes and low myopes, moderate myopes showed a significantly greater increase in IOP and higher peak values for IOP (18.6, 18.7, and 19.8 mmHg for emmetropes, low, and moderate myopes, respectively). Mean values of OPP in moderate myopes were significantly lower than in emmetropes and low myopes during HDR. Compared with baseline, mean SBP and DBP decreased obviously in emmetropes during HDR, while changes were minimal in the other groups. CONCLUSION Abnormal auto-regulation of ocular blood pressure in myopes of moderate and greater severity may pose a risk factor for developing ocular hypertension and possibly glaucoma when exposed to microgravity. HDR may offer a method of screening candidates for spaceflight for this risk prior to microgravity exposure.

Behavioral phenotypic properties of a natural occurring rat model of congenital stationary night blindness with Cacna1f mutation.

Cacna1f gene mutation could lead to incomplete congenital stationary night blindness (iCSNB) disease. The CSNB-like phenotype rat is a spontaneous rat model caused by Cacna1f gene mutation. The present study explored the phenotypic properties of behavior performance in CSNB rats further. The vision-related behaviors of CSNB rats were assessed with a Morris water maze (MWM), passive avoidance tests, and open-field test. Motor ability was evaluated with a rotarod test and a wire hang test, and mechanical pain and thermalgia were used to evaluate sensory system function. Electroretinograms (ERGs) were recorded to evaluate the function of the retina. The vision-related results showed that longer latencies of escape and reduced probe trial in MWM for CSNB rats. There were more errors in avoidance test; CSNB rats were more active in the open field and presented a different pattern of exploration. The locomotor-related behaviors showed shorter falling latencies in the rotarod test and shorter gripping time in CSNB rats. And mechanical thresholds of pain increased in CSNB rats. The ERGs indicated that both the amplitude and latency of rod and cone systems were impaired in the CSNB rats. In summary, Cacna1f gene mutation changed the performance of various behaviors in the CSNB rat aside from vision-related phenotype. Cacna1f gene might play a role in a wide range of responses in the organism. These results confirm the importance of a comprehensive profile for understanding the behavior phenotype of Cacna1f gene mutation in CSNB rat.

Properties of Flicker ERGs in Rat Models with Retinal Degeneration.

Purpose. To describe the characteristics of rod and cone functions in rat models for congenital stationary night blindness (CSNB) and retinal cone dysfunction (RCD). Methods. Rod and cone function were isolated by recording the rod-/cone-driven flicker and blue light flicker electroretinograms (ERGs). Results. During dark adaptation, the amplitudes of flicker ERGs in CSNB rats were lower than those in control rats; the responses of RCD rats were similar to control rats. During light adaptation, the amplitudes of flicker ERGs in CSNB rats were reduced; whereas the responses of RCD rats were not detected. Blue flicker ERGs were not observed in CSNB rats at lower frequencies. The cone driven critical flicker frequencies (CFFs) in control rats were 62 Hz. The rod driven CFF of RCD rats was 20 Hz; whereas the rod-/cone-driven CFF of CSNB rats both were about 25 Hz. Conclusions. The function of the rod system was damaged completely, the cones were the source of vision in CSNB rats. Rod system function is excellent in RCD rat. The rods of albinism rats are sensitive to frequencies less than 20 Hz; whereas the cones are sensitive to frequencies up to 62 Hz.