Age-related macular degeneration (AMD), characterized by progressive degeneration of retinal pigment epithelium (RPE), is the major cause of irreversible blindness and visual impairment in elderly population. We previously established a RPE degeneration model using an acute high dose sodium iodate to induce oxidative stress. Here we report findings on a prolonged treatment of low doses of sodium iodate on human RPE cells (ARPE-19). RPE cells were treated continuously with low doses (2–10 mM) of sodium iodate for 5 days. Low doses (2–5 mM) of sodium iodate did not reduce RPE cell viability, which is contrasting to cell apoptosis in 10 mM treatment. These low doses are sufficient to retard RPE cell migration and reduced expression of cell junction protein ZO-1. Phagocytotic activity of RPE cells was attenuated by sodium iodate dose-dependently. Sodium iodate also increased expression of FGF-2, but suppressed expression of IL-8, PDGF, TIMP-2 and VEGF. Furthermore, HTRA1 and epithelial-to-mesenchymal transition marker proteins were downregulated, whereas PERK and LC3B-II proteins were upregulated after sodium iodate treatment. These results suggested that prolonged exposure to non-lethal doses of oxidative stress induces RPE cell dysfunctions that resemble conditions in AMD. This model can be used for future drug/treatment investigation on AMD.

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Continuous exposure to non-lethal doses of sodium iodate induces retinal pigment epithelial cell dysfunction.

Diabetic retinopathy (DR) is one of the common microvascular complications of diabetes mellitus, which is the main cause of blindness in diabetic patients. Angiogenesis plays an important role in retinal detachment and retinal microvascular inflammation throughout the whole development of DR. This study aimed to investigate the regulatory effect and the potential mechanism of miR-377 on high glucose and hypoxia-induced angiogenesis and inflammation in human retinal endothelial cells, and found that the miR-377 level was significantly increased after high glucose and hypoxia-mimetic agent to simulate the DR milieu. Moreover, miR-377 was confirmed to directly decrease target SIRT1 gene, further aggravated proliferation, cell cycle transition, migration and angiogenesis, pro-inflammatory molecules release induced by high glucose and hypoxia in vitro. Conversely, down-regulation of miR-377 enhanced expression of SIRT1 and in turn alleviated high glucose and hypoxia-induced angiogenesis and inflammation in vitro. Additionally, Western blot results showed that down-regulation of miR-377 restrained high glucose and hypoxia-induced protein expressions of p-IκBα, nuclear P65 and p-P65. Conversely, up-regulation of miR-377 presented opposite results. Conclusively, down-regulation of miR-377 could partially suppress high glucose and hypoxia-induced angiogenic functions, restrain pro-inflammatory cytokines release, and its mechanism may though inhibition of NF-κB pathway by direct up-regulation of target gene SIRT1 expression. Our study suggests that miR-377 may be used as a potential novel target for prevention strategy for DR.

Down-regulation of miR-377 suppresses high glucose and hypoxia-induced angiogenesis and inflammation in human retinal endothelial cells by direct up-regulation of target gene SIRT1.

Incorporation of permeation enhancers is one of the most widely employed approaches for delivering drugs across biological membranes. Permeation enhancers aid in delivering drugs across various physiological barriers such as brain capillary endothelium, stratum corneum, corneal epithelium, and mucosal membranes that pose resistance to the entry of a majority of drugs. Borneol is a natural, plant-derived, lipophilic, volatile, bicyclic monoterpenoid belonging to the class of camphene. It has been used under the names "Bing Pian" or "Long Nao" in Traditional Chinese Medicine for more than 1000 years. Borneol has been incorporated predominantly as an adjuvant in the traditional Chinese formulations of centrally acting drugs to improve drug delivery to the brain. This background knowledge and anecdotal evidence have led to extensive research in establishing borneol as a permeation enhancer across the blood-brain barrier. Alteration in cell membrane lipid structures and modulation of multiple ATP binding cassette transporters as well as tight junction proteins are the major contributing factors to blood-brain barrier opening functions of borneol. Owing to these mechanisms of altering membrane properties, borneol has also shown promising potential to improve drug delivery across other physiological barriers as well. The current review focuses on the role of borneol as a permeation enhancer across the blood-brain barrier, mucosal barriers including nasal and gastrointestinal linings, transdermal, transcorneal, and blood optic nerve barrier.

Borneol: a Promising Monoterpenoid in Enhancing Drug Delivery Across Various Physiological Barriers

Circulating hematopoietic stem cells in patients with neovascular age-related macular degeneration

To investigate the ameliorate effect and underlying mechanism of Xueshuantong for Injection (Lyophilized, 注射用血栓通, XST) in streptozocin (STZ)-induced diabetic retinopathy (DR) rats. Diabetes mellitus (DM) model was induced by intraperitoneal (i.p.) injection of STZ (60 mg/kg) in Sprague-Dawley rats. Diabetic rats were randomized into 3 groups (n=10) according to a random number table, including DM, XST50 and XST100 groups. XST treatment groups were daily i.p. injected with 50 or 100 mg/kg XST for 60 days, respectively. The control and DM groups were given i.p. injection with saline. Blood glucose level and body weight were recorded every week. Histological changes in the retina tissues were observed with hematoxylin-eosin staining. Apoptosis and inflammation related factors, including cleaved caspase-3, glial fifibrillary acidic protein (GFAP), tumor necrosis factor-α (TNF-α) and intercellular cell adhesion molecule-1 (ICAM-1) were detected by Western blot or real-time polymerase chain reaction. Then, the levels of advanced glycation end product (AGE) and its receptor (RAGE) were investigated. Tight junctions proteins (Zonula occludens-1 (ZO-1), Occludin and Claudin-5) of blood-retinal barrier were detected by Western blot. The levels of retinal fifibrosis, transforming growth factor-β1 (TGF-β1)-Smad2/3 signaling pathway were evaluated at last. There was no signifificant difference in the body weight and blood glucose level between XST and DM groups (P>0.05). Compared with the DM group, XST treatment signifificantly increased the retinal thickness of rats (P<0.05 or P<0.01), and suppressed cleaved caspase-3 expression (P<0.01). XST increased the protein expressions of ZO-1, Occludin and Claudin-5 and decreased the mRNA expressions of matrix metalloproteinase 2 (MMP-2) and MMP-9 (P<0.05 or P<0.01). Moreover, XST signifificantly reduced the productions of AGE and RAGE proteins in the retina of rats (P<0.05 or P<0.01), suppressed the over-expression of TNF-α, and decreased the elevated level of ICAM-1 in retina of rats (P<0.05 or P<0.01). XST signifificantly reduced the levels of α-smooth muscle actin (α-SMA), connective tissue growth factor (CTGF), TGF-β1 and phosphorylation of Smad2/3 protein in rats (P<0.05 or P<0.01). XST had protective effects on DR with possible mechanisms of inhibiting the inflammation and apoptosis, up-regulating the expression of tight junction proteins, suppressing the productions of AGE and RAGE proteins, and blocking the TGF-β/Smad2/3 signaling pathway. XST treatment might play a role for the future therapeutic strategy against DR.

Xueshuantong for Injection (Lyophilized, ) Alleviates Streptozotocin-Induced Diabetic Retinopathy in Rats.

Objective
To observe the contribution of Borneolum syntheticum to the intervention effect of Liuwei Dihuang Pill (六味地黄丸, LDP) on experimental retinal degeneration, and initially investigate the mechanism of Borneolum syntheticum as meridian-lead-in drug.

Contribution of Borneolum syntheticum to the Intervention Effect of Liuwei Dihuang Pill () on Experimental Retinal Degeneration.

Objective: The objective of this study is to investigate the inhibitory effect of LXHY, a Chinese medicine compound formula, on choroidal neovascularization (CNV) and to find the possible working mechanism. Methods: CNV was induced in C57BL/6 mice by krypton laser and bone marrow-derived cells (BMCs) isolated from enhanced green fluorescent protein (EGFP) transgenic mice were injected through tail vein 0.5–1 h after the laser surgery. The BMC-treated mice were randomly divided into two groups gavaged with either distilled water (DW group) or LXHY formula solution from day 1 after laser surgery. On days 7, 14, and 28 after treatment, histopathologic examination, fundus fluorescein angiography, and choroidal flatmount assay were performed to measure the CNV severity and BMC recruitment. CXCR4 levels in peripheral blood were measured by enzyme-linked immunosorbent assay. Stromal cell-derived factor-1α (SDF-1α), vascular cell adhesion molecule-1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1) were detected by immunofluorescent staining. Results: On days 7 and 14 after treatment, CNV lesions in the LXHY-treated mice showed less recruitment of BMCs and were smaller in size compared to DW-treated mice. Histological examination also confirmed less severe CNV lesions in the LXHY group. CXCR4 levels in peripheral blood in the LXHY group were less than that of DW group on days 7 and 14. Moreover, the expression levels of SDF-1α, ICAM-1, and VCAM-1 at the lesion sites in the LXHY group were lower compared with the DW group. Conclusion: This experiment indicated that LXHY formula could inhibit CNV formation and development, probably by inhibiting the recruitment and attachment of BMCs into CNV area.

LXHY formula inhibits choroidal neovascularization development via inhibiting the recruitment and adhesion of BMCs to the retina

Atractylenolide III from Atractylodes macrocephala Koidz promotes the activation of brown and white adipose tissue through SIRT1/PGC-1α signaling pathway.

Pyruvate Dehydrogenase Kinase 2 Accelerates Endotoxin Shock by Promoting Mitogen-Activated Protein Kinase Activation

The utility model relates to an ophthalmology medical experiment technical field especially relates to a chronic experiment nature retina light injury experimental apparatus, which comprises a bracket, be equipped with at least one deck illumination board in the support, the lower fixed surface of illumination board has the LED light source for the simulation sunlight, glazed adjusting device is connected to the LED light source, is used for adjusting the experimental regional illuminance in illumination board below. When experimental, place the animal experiment cage experimental regional, realize the research to chronic retina light injury through adjusting illuminance and time. Experimental go on in having the darkroom of normal ventilation can, the support does not have all around andshelters from, feeds experimental animal in the long -time process of the test of being convenient for and eats hello water, compare in prior art the experimental apparatus and directly make the darkroom, simple structure, the test operation is more convenient.

Qun-Ying Ma

Papers

Contribution of Borneolum syntheticum to the Intervention Effect of Liuwei Dihuang Pill () on Experimental Retinal Degeneration.

LXHY formula inhibits choroidal neovascularization development via inhibiting the recruitment and adhesion of BMCs to the retina

Atractylenolide III from Atractylodes macrocephala Koidz promotes the activation of brown and white adipose tissue through SIRT1/PGC-1α signaling pathway.

Pyruvate Dehydrogenase Kinase 2 Accelerates Endotoxin Shock by Promoting Mitogen-Activated Protein Kinase Activation

Chronic experiment nature retina light injury experimental apparatus