Iodoacetic acid (IAA) has been applied to different species to acutely induce photoreceptor degeneration. The purpose of the present study was to use this toxin to thoroughly eliminate photoreceptors and induce complete blindness in the cat. IAA was delivered by single ear vein injection (20 mg kg−1). Six months after the IAA treatment, functional evaluations including pupillary light reflex (PLR), electroretinogram (ERG), visual behavior tests were performed. Morphological examinations were carried out after the functional evaluation. The present result shows that, six months after the IAA application, animals lost visual functions and became completely blind. High dose IAA application via ear vein delivery created an acute and reliable complete photoreceptor degeneration model in the cat. This model can be applied to genetic and cellular therapies for visual function restoration.
Abstract Our purpose was to find a method to create a large animal model of inducible photoreceptor damage. To this end, we tested in domestic swine the efficacy of two chemical toxins, known to create photoreceptor damage in other species: Iodoacetic Acid (IAA) and Sodium Iodate (NaIO 3 ). Intravenous (IV) administration of NaIO 3 up to 90 mg/kg had no effect on retinal function and 110 mg/kg was lethal. IV administration of IAA (5–20 mg/kg) produced concentration-dependent changes in visual fu...
Retinitis pigmentosa (RP) and age-related macular degeneration (AMD) represent two major retinal degenerative diseases that lead progressively to blindness. Both RP and AMD target photoreceptors constituting the outer retina. Unlike lower vertebrates, the retina in higher vertebrates, including humans, is not significantly regenerated after injury or disease, leading to an interest in stem cell transplantation therapy to restore damaged photoreceptors. The cause of AMD has yet to be uncovered, a...
Abstract Iodoacetic acid (IAA) induces photoreceptor (PR) degeneration in small animal models, however, eye size and anatomic differences detract from the usefulness of these models for studying retinal rescue strategies intended for humans. Porcine eyes are closer in size to human eyes and have a rich supply of rod and cones. This study investigated whether IAA also produced PR degeneration in the porcine retina, whether the damage was preferential for rods or cones, and whether IAA induced rem...
Background Recent research on macular disease has prompted investigation into the condition of the intersection of the inner and outer segments (IS/OS) and its relationship with retinal photoreceptor abnormalities. Because the relationship between optical coherence tomography (OCT) images and histopathology is unclear, we compared these in an iodoacetic acid (IAA)-induced model of photoreceptor degeneration in rabbits. Methods IAA (20 mg/kg), which is toxic to photoreceptors, was injected into s...
Purpose. To elucidate the gene defect in a pedigree of cats segregating for autosomal dominant rod–cone dysplasia (Rdy), a retinopathy characterized extensively from a clinical perspective. Disease expression in Rdy cats is comparable to that in young patients with congenital blindness (Leber congenital amaurosis [LCA] or retinitis pigmentosa [RP]).
Last. Mingliang Pu(PKU: Peking University)H-Index: 25
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PURPOSE: To evaluate early changes in the visual response properties of Y cells in the detached feline retina. METHODS: The retinas of young adult cats were detached by injection, with a glass micropipette, of a solution of 0.004% sodium hyaluronate in a balanced salt solution between the neural retina and the retinal pigment epithelium. At 1, 3, and 7 days after detachment, the eyes were removed. The eyecup was prepared as a flat mount in a recording chamber and superfused with medium. Extracel...
#2Shin H. Kang(Johns Hopkins University)H-Index: 20
Last. King Wai Yau(JHUSOM: Johns Hopkins University School of Medicine)H-Index: 88
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Intrinsically photosensitive retinal ganglion cells sense and transmit light information to brain centres that control non-image-forming visual functions, such as the pupillary light reflex and circadian photoentrainment. This paper describes the biophysical properties of these melanopsin-containing cells. It is found that single-photons of light are sufficient to elicit large and prolonged responses.
Last. Samer Hattar(Johns Hopkins University)H-Index: 37
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The mammalian retina has three types of light-sensing cells: rods, cones and melanopsin-containing cells. Rods and cones are involved in vision but have also been shown to contribute to light-entrainment of the circadian clock. Rods and cones must signal through melanopsin-containing cells for the latter.
This study investigated the anatomical consequences of a photoreceptor toxin, iodoacetic acid (IAA), in the rabbit retina. Retinae were examined 2 weeks, 1, 3, and 6 months after systemic IAA injection. The retinae were processed using standard histological methods to assess the gross morphology and topographical distribution of damage, and by immunohistochemistry to examine specific cell populations in the retina. Degeneration was restricted to the photoreceptors and was most common in the vent...
PURPOSE. An early-onset retinal degenerative disease has been identified in Persian cats. This study genetically, clinically, and histologically characterized the disease. A breeding colony was established to assist with identification of the causative gene and to provide a resource for vision research. METHODS. Cats were produced from testcross breedings. Kittens underwent serial ophthalmic and neuro-ophthalmic examinations. Globes were harvested from age-matched affected, obligate carrier, and...
Background: Retinal degenerative disorders (RDs) are the main cause of blindness without curable treatment. Our previous studies have demonstrated that human-induced pluripotent stem cells can differentiate into retinal organoids with all subtypes of retina, which provides huge promise for treating these diseases. Before these methods can be realized, RD animal models are required to evaluate the safety and efficacy of stem cell therapy and to develop the surgical tools and procedures for cell t...
Abstract Porcine models of ophthalmological diseases are often used in pre-clinical translational studies due to pigs’ similarities to humans. In particular, the iodoacetic acid (IAA) model of photoreceptor degeneration seems to mimic well the endstage phenotype of human pathologies as retinitis pigmentosa and age-related macular degeneration, with high potential for prosthesis/retinal devices testing. IAA is capable of inducing photoreceptor death by blockage of glycolysis, and its effects on t...
PURPOSE: We investigated structural changes in the retina by using optical coherence tomography (OCT) in a feline model of retinal degeneration using iodoacetic acid (IAA). METHODS: We examined 22 eyes of 11 felines over 2 years of age. The felines had fasted for 12 hours and were intravenously injected with IAA 20 mg/kg of body weight. OCT (Spectralis OCT) was performed at the point where the ends of the retinal vessels collected in the lateral direction from the optic nerve head and area centr...
Last. Biju B. Thomas(SC: University of Southern California)H-Index: 18
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Dysfunction and death of retinal pigment epithelium (RPE) and or photoreceptors can lead to irreversible vision loss. The eye represents an ideal microenvironment for stem cell-based therapy. It is considered an “immune privileged” site, and the number of cells needed for therapy is relatively low for the area of focused vision (macula). Further, surgical placement of stem cell-derived grafts (RPE, retinal progenitors, and photoreceptor precursors) into the vitreous cavity or subretinal space ha...