Phototransduction in a Rabbit Model with Retinitis Pigmentosa


Austin J Clin Ophthalmol. 2018; 5(3): 1095.

Phototransduction in a Rabbit Model with Retinitis Pigmentosa

Asakawa K* and Ishikawa H

Department of Orthoptics and Visual Science, Kitasato University, School of Allied Health Sciences, Kanagawa, Japan

*Corresponding author: Ken Asakawa, Department of Orthoptics and Visual Science, Kitasato University, School of Allied Health Sciences, 1-15-1 Kitasato, Sagamihara, Minami-ku, Kanagawa 252-0373, Japan

Received: July 31, 2018; Accepted: August 21, 2018; Published: August 28, 2018


Retinitis pigmentosa (RP) is a progressive disease that exhibits abnormalities in the photoreceptor cells of the rods and cones that detect light, and is characterized by symptoms such as night blindness, visual field constriction especially in the peripheral field, and reduced visual acuity [1]. In Japan, this disorder is estimated to affect approximately 20 in 100,000 people and is the third leading cause of blindness following glaucoma and diabetic retinopathy [2]. RP appears through a variety of genetic inheritance modes, including autosomal dominant, autosomal recessive, and X-linked recessive patterns, and 40 or more causative genes have been identified [3]. In many patients, however, genetic abnormalities cause this disorder to be under diagnosed.

To overcome these difficulties, transgenic (Tg) rabbits with a P347L rhodopsin mutation were created by Kondo et al. [4]. They displayed symptoms extremely similar to findings in patients with RP and are considered to offer a useful animal model for elucidating the pathology of RP [5]. However, when and where the degeneration begins are unclear, as are its underlying mechanisms and pathologies. There are many other unknown issues as well, such as how light is received and converted to electric signals in the steps leading to blindness, and why organisms with undeveloped vision such as rabbits receive light, and where photoreceptors are located in these animals. In humans, light is received by photoreceptor cells and is converted to electric signals to visualize an object.

In clinical settings, we encounter patients with RP who maintain circadian rhythms in which the body wakes in the morning and becomes sleepy at night, and those who present a residual light response in which the pupil becomes smaller on exposure to light. This is unlike patients who have lost their vision due to other eye diseases. In other words, RP patients show partial response to light even when blind and unable to sense light. Based on these facts, we hypothesized the existence of photoreceptors other than the rods and cones of the photoreceptor cells. In this review based on our previous studies [6,7], we report the mechanism of retinal degeneration and describe the process of phototransduction in Tg rabbits with a P347L rhodopsin mutation.

Pupil Response

The photoreceptor cells control the constriction and dilation of the pupil in response to change in light stimulus, namely the pupil response. Figure 1 shows (A) the percentage pupil constriction results to red light (635nm) and (B) blue light (470nm) with intensity of 2.3 log cd/m2 for 60s in the Wild-type (WT) and Tg rabbits. The mean values at 4 months was 20.8% for red light and 61.1% for blue light in the WT rabbits and 19.6% for red light and 59.4% for blue light in the Tg rabbits. The differences between the two types were not significant (red, p=0.66; blue, p=0.45, Mann-Whitney U test). At 8 months, the red light was slightly reduced in the Tg rabbits (13.8%). This value was significantly lower than that of the WT rabbits (28.5%; p<0.01). The values for the WT rabbits at 12 months were 25.0% for red light and 56.2% for blue light, whereas the Tg rabbits indicated a loss of response to red light (6.1%); however, pupil constriction to blue light was still induced (20.3%). The values for the Tg rabbits were also significantly smaller than those of the WT rabbits (red and blue, p<0.01). At 24 months, pupil constriction even in blue light stimulus was eliminated (7.9%).