Functional Changes in Inner Retinal Neurons in Animal Models of Photoreceptor Degeneration

Author(s):  
Theresa Puthussery ◽  
W. Rowland Taylor
2019 ◽  
Vol 2019 ◽  
pp. 1-16 ◽  
Author(s):  
Mitsuru Nakazawa ◽  
Aiko Hara ◽  
Sei-ichi Ishiguro

Purpose. The aim of this study was to understand the relationship between the findings of spectral-domain optical coherence tomography (SD-OCT) of previously reported animal models of retinitis pigmentosa (RP) associated with known genetic mutations and their background structural and functional changes. Methods. We reviewed previous publications reporting the SD-OCT findings of animal models of RP and summarized the characteristic findings of SD-OCT in nine different animal models (RCS–/–, RHO P23H, RHO S334ter, RHO–/–, Rpe65–/–, rp12, Pde6β–/– (rd1 and rd10), and Arr1–/–) of human RP. Results. Despite the various abnormal structural changes found in these different animal models, progressive thinning of the outer nuclear layer (ONL) and hyperreflective change in the inner and outer segment (IS-OS) layers of the photoreceptors were commonly observed on SD-OCT. In the rapidly progressive severe photoreceptor degeneration seen in rd10 and Arr1–/– mice, the ONL appeared hyperreflective. Electroretinography revealed various degrees of disease severity in these animal models. Discussion and Conclusion: SD-OCT is sensitive enough to detect even mild changes in the photoreceptor OS. Conversely, SD-OCT cannot qualitatively differentiate the pathologic and functional differences in the photoreceptors associated with different genetic abnormalities, with the exception of the rapid progression of severe forms of photoreceptor degeneration. These findings can be of value to understand better the clinical findings and the heterogeneous degenerative processes in patients with RP.


Neuroscience ◽  
2018 ◽  
Vol 372 ◽  
pp. 141-153 ◽  
Author(s):  
Yuxiang Yuan ◽  
Ying Zhu ◽  
Yinwei Song ◽  
Yin Zhao ◽  
Xiaoqin Yan ◽  
...  

2020 ◽  
Vol 21 (19) ◽  
pp. 7252
Author(s):  
Johnny Di Pierdomenico ◽  
Diego García-Ayuso ◽  
María Elena Rodríguez González-Herrero ◽  
David García-Bernal ◽  
Miguel Blanquer ◽  
...  

Inherited photoreceptor degenerations are not treatable diseases and a frequent cause of blindness in working ages. In this study we investigate the safety, integration and possible rescue effects of intravitreal and subretinal transplantation of adult human bone-marrow-derived mononuclear stem cells (hBM-MSCs) in two animal models of inherited photoreceptor degeneration, the P23H-1 and the Royal College of Surgeons (RCS) rat. Immunosuppression was started one day before the injection and continued through the study. The hBM-MSCs were injected in the left eyes and the animals were processed 7, 15, 30 or 60 days later. The retinas were cross-sectioned, and L- and S- cones, microglia, astrocytes and Müller cells were immunodetected. Transplantations had no local adverse effects and the CD45+ cells remained for up to 15 days forming clusters in the vitreous and/or a 2–3-cells-thick layer in the subretinal space after intravitreal or subretinal injections, respectively. We did not observe increased photoreceptor survival nor decreased microglial cell numbers in the injected left eyes. However, the injected eyes showed decreased GFAP immunoreactivity. We conclude that intravitreal or subretinal injection of hBM-MSCs in dystrophic P23H-1 and RCS rats causes a decrease in retinal gliosis but does not have photoreceptor neuroprotective effects, at least in the short term. However, this treatment may have a potential therapeutic effect that merits further investigation.


2019 ◽  
Vol 20 (1) ◽  
pp. 220 ◽  
Author(s):  
Sandesh Reddy ◽  
Iyan Younus ◽  
Vidya Sridhar ◽  
Doodipala Reddy

This article provides an overview of neuroimaging biomarkers in experimental epileptogenesis and refractory epilepsy. Neuroimaging represents a gold standard and clinically translatable technique to identify neuropathological changes in epileptogenesis and longitudinally monitor its progression after a precipitating injury. Neuroimaging studies, along with molecular studies from animal models, have greatly improved our understanding of the neuropathology of epilepsy, such as the hallmark hippocampus sclerosis. Animal models are effective for differentiating the different stages of epileptogenesis. Neuroimaging in experimental epilepsy provides unique information about anatomic, functional, and metabolic alterations linked to epileptogenesis. Recently, several in vivo biomarkers for epileptogenesis have been investigated for characterizing neuronal loss, inflammation, blood-brain barrier alterations, changes in neurotransmitter density, neurovascular coupling, cerebral blood flow and volume, network connectivity, and metabolic activity in the brain. Magnetic resonance imaging (MRI) is a sensitive method for detecting structural and functional changes in the brain, especially to identify region-specific neuronal damage patterns in epilepsy. Positron emission tomography (PET) and single-photon emission computerized tomography are helpful to elucidate key functional alterations, especially in areas of brain metabolism and molecular patterns, and can help monitor pathology of epileptic disorders. Multimodal procedures such as PET-MRI integrated systems are desired for refractory epilepsy. Validated biomarkers are warranted for early identification of people at risk for epilepsy and monitoring of the progression of medical interventions.


2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Angela C. Gauthier ◽  
Ji Liu

Glaucoma is the most common cause of irreversible blindness worldwide. This neurodegenerative disease becomes more prevalent with aging, but predisposing genetic and environmental factors also contribute to increased risk. Emerging evidence now suggests that epigenetics may also be involved, which provides potential new therapeutic targets. These three factors work through several pathways, including TGF-β, MAP kinase, Rho kinase, BDNF, JNK, PI-3/Akt, PTEN, Bcl-2, Caspase, and Calcium-Calpain signaling. Together, these pathways result in the upregulation of proapoptotic gene expression, the downregulation of neuroprotective and prosurvival factors, and the generation of fibrosis at the trabecular meshwork, which may block aqueous humor drainage. Novel therapeutic agents targeting these pathway members have shown preliminary success in animal models and even human trials, demonstrating that they may eventually be used to preserve retinal neurons and vision.


2002 ◽  
Vol 3 (4) ◽  
pp. 217-231 ◽  
Author(s):  
Subrata Chakrabarti ◽  
Zia Ali Khan ◽  
Mark Cukiernik ◽  
Gen Fukuda ◽  
Shali Chen ◽  
...  

Endothelin (ET) peptides perform several physiological, vascular, and nonvascular functions and are widely distributed in a number of tissues. They are altered in several disease processes including diabetes. Alteration of ETs have been demonstrated in organs of chronic diabetic complications in both experimental and clinical studies. The majority of the effects of ET alteration in diabetes are due to altered vascular function. Furthermore, ET antagonists have been shown to prevent structural and functional changes induced by diabetes in animal models. This review discusses the contribution of ETs in the pathogenesis and the potential role of ET antagonism in the treatment of chronic diabetic complications.


2019 ◽  
Vol 5 (1) ◽  
pp. 15-45 ◽  
Author(s):  
Jennifer J. Hunter ◽  
William H. Merigan ◽  
Jesse B. Schallek

Retinal function has long been studied with psychophysical methods in humans, whereas detailed functional studies of vision have been conducted mostly in animals owing to the invasive nature of physiological approaches. There are exceptions to this generalization, for example, the electroretinogram. This review examines exciting recent advances using in vivo retinal imaging to understand the function of retinal neurons. In some cases, the methods have existed for years and are still being optimized. In others, new methods such as optophysiology are revealing novel patterns of retinal function in animal models that have the potential to change our understanding of the functional capacity of the retina. Together, the advances in retinal imaging mark an important milestone that shifts attention away from anatomy alone and begins to probe the function of healthy and diseased eyes.


JCI Insight ◽  
2020 ◽  
Vol 5 (2) ◽  
Author(s):  
Bristol Denlinger ◽  
Zachary Helft ◽  
Michael Telias ◽  
Henri Lorach ◽  
Daniel Palanker ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document