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Biomedicine & Pharmacotherapy =... Jun 2020Photoreceptor cells are first-order retinal neurons that directly contribute to the formation of vision. Photoreceptor degeneration is the primary cause of vision...
Photoreceptor cells are first-order retinal neurons that directly contribute to the formation of vision. Photoreceptor degeneration is the primary cause of vision impairment during the course of retinopathies such as retinitis pigmentosa and age-related macular degeneration, for which photoreceptor-targeted therapies are currently unavailable. Shihu Yeguang Pill (SYP), a classic formula in traditional Chinese medicine, has a long histology of clinical application for the treatment of a wide range of retinopathies in China. However, whether SYP is pharmacological effective at protecting photoreceptor cells is unclear. The current study thus directly addressed the pharmacological implications of SYP in photoreceptor degeneration in a mouse model characterized by bright light-induced retinal degeneration. Non-invasive full-retinal assessment was carried out to evaluate the effect of SYP on the retinal structure and function through optical coherence tomography and electroretinography, respectively. In addition, photoreceptor apoptosis, second-order neuron impairment and reactive changes in retinal microglial and müller cells, hallmark pathologies associated with photoreceptor degeneration, were assessed using immunohistochemistry and real-time PCR analyses. The results showed that SYP treatment attenuated bright light-induced impairment of the retinal structure and function. Moreover, SYP treatment suppressed photoreceptor apoptosis, alleviated the impairment of bipolar and horizontal cells and mitigated the reactive changes of müller and microglial cells in the bright light-exposed retinas. Real-time PCR analyses showed that dysregulated expression of pro-apoptotic c-fos and c-jun and anti-apoptotic bcl-2 as well as proinflammatory TNF-α in the bright light-exposed retinas was partially normalized as a result of SYP treatment. In summary, the work here demonstrates for the first time that SYP treatment protects the retinas from developing bright light-induced photoreceptor degeneration and associated alterations in second-order neurons and glial cells. The findings here thus provide experimental evidence to better support the mechanism-guided clinical application of SYP in the treatment of related retinal degenerative diseases.
Topics: Animals; Apoptosis; Drugs, Chinese Herbal; Electroretinography; Female; Light; Medicine, Chinese Traditional; Mice, Inbred BALB C; Photoreceptor Cells; Photoreceptor Cells, Vertebrate; Retina; Retinal Degeneration
PubMed: 32135462
DOI: 10.1016/j.biopha.2020.110050 -
Current Opinion in Neurobiology Oct 1993A variety of genetic and environmental factors cause degeneration of retinal photoreceptors. This review focuses on current strategies to rescue defective, but still... (Review)
Review
A variety of genetic and environmental factors cause degeneration of retinal photoreceptors. This review focuses on current strategies to rescue defective, but still viable, rods and cones, including transplantation of normal retinal pigment epithelium cells, corrective gene therapy, administration of survival/growth factors, protection from the damaging effects of light, and dietary supplementation of vitamin A.
Topics: Animals; Cell Transplantation; Genetic Therapy; Humans; Light; Photoreceptor Cells; Pigment Epithelium of Eye; Retinal Degeneration; Vitamin A
PubMed: 8260832
DOI: 10.1016/0959-4388(93)90156-s -
Experimental Eye Research Jun 1989In this study retinas of pink-eyed 26 day-old RCS dystrophic rats were injected with normal, melanotic retinal pigment epithelial (RPE) cells into the subretinal space....
In this study retinas of pink-eyed 26 day-old RCS dystrophic rats were injected with normal, melanotic retinal pigment epithelial (RPE) cells into the subretinal space. The areas containing underlying photoreceptor cells were subsequently investigated by electron microscopy at 60 days and light microscopy immunocytochemistry at 60 and 120 days. Retinal regions containing viable RPE-cell grafts exhibited melanin-contained RPE cell transplants attached to Bruch's membrane and containing shed rod outer segments (ROS). Also, the ROS of these photoreceptor cells exhibited a normal-appearing structural relationship with apical membrane projections of these RPE cells. The debris zone, prominent in retinas of 60 day-old RCS dystrophic rats, was much reduced in RPE-cell grafted regions. By at least 3 months after RPE transplantation, immunostaining for Na+,K+-ATPase was demonstrated along inner segments (IS) of photoreceptor cells in grafted regions, as was also shown in control retinas, but not in non-grafted regions. Opsin immunostaining in RPE-cell grafted regions and in control retinas was detected along ROS and rod inner segments (RIS) and at the periphery of cell bodies in the outer nuclear layer. This study has shown that transplanted normal RPE cells in retinas of RCS dystrophic rats appear to have normal functional and structural characteristics at least three months after transplantation. Furthermore, the rescued PRC's exhibited a normal distribution of and immunostaining density for the membrane-bound enzyme Na+,K+-ATPase and the photo-pigment opsin.
Topics: Animals; Eye Proteins; Microscopy, Electron; Photoreceptor Cells; Pigment Epithelium of Eye; Rats; Retinal Degeneration; Retinal Pigments; Rod Opsins; Sodium-Potassium-Exchanging ATPase
PubMed: 2543586
DOI: 10.1016/0014-4835(89)90067-5 -
Neurochemical Research Apr 1997Lipid metabolism in photoreceptor rod outer segments has attracted considerable attention because of its importance in providing the appropriate environment for... (Review)
Review
Lipid metabolism in photoreceptor rod outer segments has attracted considerable attention because of its importance in providing the appropriate environment for supporting an efficient phototransduction mechanism. Recent studies suggest that lipid metabolism in these membranes is involved in the generation of second messengers and in signal transduction mechanisms. Phospholipid turnover is tightly regulated by phosphorylation-dephosphorylation reactions and light, and provides, in turn, with molecules capable of activating protein kinases and cellular processes such as membrane fusion or light-adaptation. These findings suggest that photoreceptor membrane lipids are more than just important structural components of the visual cell rod outer segment.
Topics: Animals; Cell Membrane; Light; Lipid Metabolism; Phospholipids; Phosphorylation; Photoreceptor Cells; Rod Cell Outer Segment
PubMed: 9130255
DOI: 10.1023/a:1027359727263 -
Current Biology : CB Feb 2005Photoreceptor cells of vertebrate eyes are fundamentally different from those of invertebrate eyes. New work on the brain of a ragworm now suggests that ancestral... (Review)
Review
Photoreceptor cells of vertebrate eyes are fundamentally different from those of invertebrate eyes. New work on the brain of a ragworm now suggests that ancestral bilaterians possessed both types of photoreceptor cell.
Topics: Animals; Biological Evolution; Cell Surface Extensions; Eye; Invertebrates; Models, Biological; Photoreceptor Cells; Rhodopsin; Signal Transduction; Species Specificity
PubMed: 15694299
DOI: 10.1016/j.cub.2005.01.027 -
Annual Review of Biophysics and... 1974
Comparative Study Review
Topics: Animals; Birefringence; Cell Membrane; Electric Conductivity; Evaluation Studies as Topic; Fourier Analysis; Mathematics; Methods; Microscopy, Electron; Models, Biological; Molecular Conformation; Photoreceptor Cells; Rana pipiens; Retina; X-Ray Diffraction
PubMed: 4607803
DOI: 10.1146/annurev.bb.03.060174.000413 -
Biophysics of Structure and Mechanism 1982Extracellular recordings from the vacuole of photoreceptor cells of Hirudo medicinalis L. were performed using microelectrodes. The cells were adapted by white light...
Extracellular recordings from the vacuole of photoreceptor cells of Hirudo medicinalis L. were performed using microelectrodes. The cells were adapted by white light flashes given at constant intervals (20 s). Response height versus relative intensity curves obtained from the same cell in physiological saline (PS) and in bathing solutions of either a) lowered calcium contents (2 micron/1 or less) or b) raised calcium contents (15 mM/1) were compared. The cells' adaptation state in PS was operationally defined by the ratio Q = hA/hs where hA is the response height evoked by the adapting flashes, and hs is the corresponding saturation response height. Sensitivity changes were measured by the half saturation intensity shift. Lowering extracellular calcium resulted in: 1. The response height increased and the shape of the response became more rounded and prolonged. 2. The total resistance between the vacuole and outside decreased from 8.2 +/- 1.4 Momega (n = 6) in PS to 4.6 +/- 0.4 Momega (n = 5). The resistance was independent of the cells' adaptation state. 3. A change of the cells' sensitivity occurred either in direction to light adaptation or in direction to dark adaptation. It depended functionally on the ratio Q: a) if Q was less or equal to about 0.6 the cells' sensitivity increased. b) if Q was greater than 0.6 the cells' sensitivity diminished. Raising extracellular calcium decreased the sensitivity of all cells tested independent of their adaptation states in PS. The results can be interpreted under the assumptions that 1. the sensitivity of leech photoreceptor cells is inversely proportional to the intracellular free calcium concentration and 2. intracellular calcium can interact with extracellular calcium in relatively dark adapted cells whereas in relatively light adapted cells the raise of intracellular free calcium is mainly effected by a release from intracellular stores. It is assumed that a Q value of about 0.6 separates relatively light adapted cells from relatively dark adapted cells.
Topics: Acclimatization; Animals; Calcium; Leeches; Light; Mathematics; Photic Stimulation; Photoreceptor Cells; Vacuoles
PubMed: 7093431
DOI: 10.1007/BF00535458 -
The Journal of Biological Chemistry Jan 1992
Review
Topics: Amino Acid Sequence; Animals; Cattle; Molecular Sequence Data; Mutation; Photoreceptor Cells; Protein Conformation; Rhodopsin; Structure-Activity Relationship
PubMed: 1730574
DOI: No ID Found -
PloS One 2013Glucose is an important metabolic substrate of the retina and diabetic patients have to maintain a strict normoglycemia to avoid diabetes secondary effects, including...
Glucose is an important metabolic substrate of the retina and diabetic patients have to maintain a strict normoglycemia to avoid diabetes secondary effects, including cardiovascular disease, nephropathy, neuropathy and retinopathy. Others and we recently demonstrated the potential role of hypoglycemia in diabetic retinopathy. We showed acute hypoglycemia to induce retinal cell death both in vivo during an hyperinsulinemic/hypoglycemic clamp and in vitro in 661W photoreceptor cells cultured at low glucose concentration. In the present study, we showed low glucose to induce a decrease of BCL2 and BCL-XL anti-apoptotic proteins expression, leading to an increase of free pro-apoptotic BAX. In parallel, we showed that, in retinal cells, low glucose-induced apoptosis is involved in the process of autophagosomes formation through the AMPK/RAPTOR/mTOR pathway. Moreover, the decrease of LAMP2a expression led to a defect in the autophagosome/lysosome fusion process. Specific inhibition of autophagy, either by 3-methyladenine or by down-regulation of ATG5 or ATG7 proteins expression, increased caspase 3 activation and 661W cell death. We show that low glucose modifies the delicate equilibrium between apoptosis and autophagy. Cells struggled against low nutrient condition-induced apoptosis by starting an autophagic process, which led to cell death when inhibited. We conclude that autophagy defect is associated with low glucose-induced 661W cells death that could play a role in diabetic retinopathy. These results could modify the way of addressing negative effects of hypoglycemia. Short-term modulation of autophagy could be envisioned to treat diabetic patients in order to avoid secondary complications of the disease.
Topics: Animals; Apoptosis; Autophagy; Blotting, Western; Cells, Cultured; Glucose; Immunohistochemistry; Immunoprecipitation; In Situ Nick-End Labeling; Mice; Photoreceptor Cells; Reverse Transcriptase Polymerase Chain Reaction
PubMed: 24066113
DOI: 10.1371/journal.pone.0074162 -
The Journal of Biophysical and... Jan 1957Fragments of freshly obtained retinas of several vertebrate species were studied by refractometry, with reference to the structure of the rods and cones. The findings...
Fragments of freshly obtained retinas of several vertebrate species were studied by refractometry, with reference to the structure of the rods and cones. The findings allowed a reassessment of previous descriptions based mainly on fixed material. The refractometric method was used also to measure the refractice indices and to calculate the concentrations of solids and water in the various cell segments. The main quantitative data were confirmed by interference microscopy. When examined by the method of refractometry the outer segments of freshly prepared retinal rods appear homogeneous. Within a few minutes a single eccentric longitudinal fiber appears, and transverse striations may develop. These changes are attributed to imbibition of water and swelling in structures normally too small for detection by light microscopy. The central "core" of outer segments and the chromophobic disc between outer and inner segments appear to be artifacts resulting from shrinkage during dehydration. The fresh outer segments of cones, and the inner segments of rods and cones also are described and illustrated. The volumes, refractive indices, concentrations of solids, and wet and dry weights of various segments of the photoreceptor cells were tabulated. Rod outer segments of the different species vary more than 100-fold in volume and mass but all have concentrations of solids of 40 to 43 per cent. Cone outer segments contain only about 30 per cent solids. The myoids, paraboloids, and ellipsoids of the inner segments likewise have characteristic refractive indices and concentrations of solids. Some of the limitations and particular virtues of refractometry as a method for quantitative analysis of living cells are discussed in comparison with more conventional biochemical techniques. Also the shapes and refractive indices of the various segments of photoreceptor cells are considered in relation to the absorption and transmission of light. The Stiles-Crawford effect can be accounted for on the basis of the structure of cone cells.
Topics: Histological Techniques; Light; Microscopy, Interference; Photoreceptor Cells; Refractometry; Retina; Retinal Cone Photoreceptor Cells; Retinal Rod Photoreceptor Cells; Rod Cell Outer Segment
PubMed: 13416308
DOI: 10.1083/jcb.3.1.15