Lycium barbarum polysaccharides related RAGE and Aβ levels in the retina of mice with acute ocular hypertension and promote maintenance of blood retinal barrier

Our previous study verified the protective effects of Lycium barbarum polysaccharides(LBP)on retinal neurons and blood vessels in acute ocular hypertension(AOH)mice.To investigate the effect of LBP on the reactivity of retinal glial cells,an AOH mouse model was established in one eye by maintaining ocular hypertension of 90 mm Hg for 60 minutes.Either LBP solution(1 mg/kg)or phosphate-buffered saline was administrated to the mice by gavage daily,starting 7 days before the AOH insult and continuing until the mice were sacrificed for specimen collection on day 4 post-insult.After AOH insult,increased numbers of astrocytes and microglia were observed,together with decreased expression of the following glial cell biomarkers in the retinal ganglion cells of AOH mice:glial fibrillary acidic protein,glutamine synthetase,aquaporin-4,S-100 proteins,ionized calcium-binding adaptor molecule 1,amyloid precursor protein and receptor of advanced glycosylation end-products.After intervention with LBP,the above changes were significantly reduced.Remarkably,morphological remodeling of blood vessel-associated retinal astrocytes,marked by glial fibrillary acidic protein,was also observed.These results,taken together,suggest that LBP regulated the production of amyloid-βand expression of receptor of advanced glycosylation end-products,as well as mediating the activity of retinal glial cells,which may lead to the promotion of better maintenance of the blood-retinal barrier and improved neuronal survival in AOH insult.This study was approved by the Committee for the Use of Live Animals in Teaching and Research(approval No.CULTRA-#1664-08).

Smart phone apps every ophthalmologist should know about

We are living in a mobile world,where the number of medical apps is surging in recent years.Over 320000 healthcare apps are now available as shown in the latest research.The major function and potential of these apps vary,from assisting the learning and practice of clinicians as well as achieving better outcomes of patients to preventing eye diseases through the education of healthy individuals.However,based on the various features,ophthalmology apps nowadays contain a wide range of subjects and focus on dif ferent stakeholder s in the ophthalmic practice,including but not limited to doctors,patients,and researchers.Here,we review special and advanced apps that ophthalmologists will find useful in their clinical practice.

Effect of Lycium barbarum Polysaccharides on the expression of endothelin-1 and its receptors in an ocular hypertension model of rat glaucoma

Lycium barbarum, a traditional Chinese anti-aging herb, has been shown to protect retinal ganglion cells （RGCs） in a rat chronic ocular hypertension （COH） model. Here, we investigated the expression of endothelin-1 （ET-1）, a strong vasoconstrictor, and its receptors, ETA and ETB, in the COH model and assessed the effects of Lycium barbarum on the ET-1 axis. Elevated intraocular pressure （IOP） was induced in the right eye of SD rats using argon laser photocoagulation. （1） The expression of ET-1, ETA and ETB in normal and COH retinas was studied. （2） Some COH rats were fed daily with Lycium barbarum Polysaccharides （LBP） using 1 mg/kg or phosphate-buffered saline （PBS） for 3 weeks （started 1 week before photocoagulation）. The effects of LBP on the expression of ET-1 and its receptors, ETA and ETB, in COH retina were evaluated. A semi-quantitative analysis of staining intensity was used to evaluate the expression levels of ET-1, ETA and ETB in retinal vasculature. We found that （1） Under COH condition, the immunoreactivity of ET-1 was increased in retina associated with an increase of ETB receptor immunoreactivity and a decrease of ETA receptor immunoreactivity. （2） After feeding COH rats with LBP, the expression of ET-1 was decreased with an increase of ETA expression and a decrease of ETB expression in the retina, especially in RGCs. （3） By comparing the staining intensity in the vasculature of COH retina in LBP-fed group with PBS-fed group, there was a decrease in the expression of ET-1 and ETA and an increase in ETB. In summary, ET-1 expression was up-regulated in the retina in COH model. LBP could decrease the expression of ET-1 and modulate the expression of its receptors, ETA and ETB, under the condition of COH. The neuroprotective effect of LBP on RGCs might be related to its ability to regulate the ET-1-mediated biological effects on RGCs and retinal vasculature.

Exacerbated VEGF up-regulation accompanies diabetes-aggravated hemorrhage in mice after experimental cerebral ischemia and delayed reperfusion

Reperfusion therapy is the preferred treatment for ischemic stroke,but is hindered by its short treatment window,especially in patients with diabetes whose reperfusion after prolonged ischemia is often accompanied by exacerbated hemorrhage.The mechanisms underlying exacerbated hemorrhage are not fully understood.This study aimed to identify this mechanism by inducing prolonged 2-hour transient intraluminal middle cerebral artery occlusion in diabetic Ins2Akita/+mice to mimic patients with diabetes undergoing delayed mechanical thrombectomy.The results showed that at as early as 2 hours after reperfusion,Ins2Akita/+mice exhibited rapid development of neurological deficits,increased infarct and hemorrhagic transformation,together with exacerbated down-regulation of tight-junction protein ZO-1 and upregulation of blood-brain barrier-disrupting matrix metallopeptidase 2 and matrix metallopeptidase 9 when compared with normoglycemic Ins2+/+mice.This indicated that diabetes led to the rapid compromise of vessel integrity immediately after reperfusion,and consequently earlier death and further aggravation of hemorrhagic transformation 22 hours after reperfusion.This observation was associated with earlier and stronger up-regulation of pro-angiogenic vascular endothelial growth factor(VEGF)and its downstream phospho-Erk1/2 at 2 hours after reperfusion,which was suggestive of premature angiogenesis induced by early VEGF up-regulation,resulting in rapid vessel disintegration in diabetic stroke.Endoplasmic reticulum stress-related pro-apoptotic C/EBP homologous protein was overexpressed in challenged Ins2Akita/+mice,which suggests that the exacerbated VEGF up-regulation may be caused by overwhelming endoplasmic reticulum stress under diabetic conditions.In conclusion,the results mimicked complications in patients with diabetes undergoing delayed mechanical thrombectomy,and diabetes-induced accelerated VEGF up-regulation is likely to underlie exacerbated hemorrhagic transformation.Thus,suppression of the VEGF pathway could be a potential approach to allow reperfusion therapy in patients with diabetic stroke beyond the current treatment window.Experiments were approved by the Committee on the Use of Live Animals in Teaching and Research of the University of Hong Kong[CULATR 3834-15(approval date January 5,2016);3977-16(approval date April 13,2016);and 4666-18(approval date March 29,2018)].

Lycium barbarum polysaccharides and ferroptosis:jumping into the era of novel regulated cell death

Lycium barbarum polysaccharides(LBP)are the key bioactive components of Lycium barbarum(also named Gouqizi or Goji berry or wolfberry),a widely used Traditional Chinese herb for more than 2000 years.Believed to balance"yin"and"yang"within the body,Lycium barbarum is consumed for general health benefits.

Ferroptosis and glaucoma: implications in retinal ganglion cell damage and optic nerve survival

Glaucoma and visual pathway degeneration:Glaucoma is the leading cause of irreversible blindness worldwide,which leads to a progressive loss of vision.Glaucoma can be classified into two types:primary open-angle glaucoma and primary closed-angle glaucoma.Primary open-angle glaucoma can be caused by the blockage of the trabecular meshwork,and this results in elevation of the intraocular pressure(IOP),leading to retinal ganglion cell(RGC)death.However,many glaucoma patients have normal IOP;this is known as normal-tension glaucoma.Nevertheless,excitotoxic damage and oxidative stress can also lead to RGC damage in normal-tension glaucoma(Almasieh et al.,2012).Glaucomatous genes such as TIGR,OPTN,and CYP1B1 have been suggested to contribute to the pathogenesis of glaucoma.However,some glaucomatous patients may remain asymptomatic in the early,moderate,and late stages.Another type of glaucoma is primary closed-angle glaucoma.In this clinical condition,a relative pupillary block is contributed by the iris obstructing aqueous outflow.The patients may suffer from corneal swelling,headache,nausea,and blurred vision during the acute phase.

Comparison of electroretinographic responses between two different age groups of adult Dark Agouti rats

AIM: To describe and compare the differences in electroretinographic responses between two different age groups of adult Dark Agouti (DA) rats and to better understand the effect of age on retinal histology and function. METHODS: The electroretinographic responses of two different age groups of adult DA rats were compared. Animals were divided into younger adult DA rats 10-12wk (n =8) and older adult DA rats 17-19wk (n=8). Full field electroretinography (ERG) was recorded simultaneously from both eyes after dark adaption and light adaption and parameters including the positive scotopic threshold response (pSTR), negative scotopic threshold response (nSTR), scotopic a -wave, b -wave, photopic a -wave, b -wave and photopic negative response (PhNR) were compared between groups. RESULTS: The older adult rats displayed lower stimulation thresholds of the STRs (pSTR and nSTR) and higher amplitudes of pSTR, scotopic a -wave and b wave, photopic b -wave and PhNR amplitudes, with shorter implicit times. Photopic a-wave amplitudes were however higher in the younger adult rats. CONCLUSION: In summary, for the rod system, photoreceptor, bipolar cell and RGC activity was enhanced in the older adult rats. For the cone system, RGC and bipolar cell activity was enhanced, while photoreceptor activity was depressed in the older adult rats. Such age -related selective modification of retinal cell function needs to be considered when conducting ophthalmic research in adult rats.

Induction of significant intraocular pressure diurnal fluctuation in rats using a modified technique of microbead occlusion

AIM： To investigate the effect of microbead iridocorneal angle occlusion on intraocular pressure（IOP） diurnal fluctuation in rat eyes. METHODS： Male Dark Agouti（DA） rats, 8-10 week old, were each given a single intracameral injection of microbeads, followed by injection of dispersive viscoelastic solution. The right eye served as the experimental eye, while the left eye served as the control. IOP was measured twice daily postoperatively for 3 wk and compared between groups. At the end of 3 wk, the rats were sacrificed and the eyes were harvested for histological analysis and retinal ganglion cell（RGC） counting. RESULTS： After microbead injection, experimental eyes had significantly higher dark time IOP than controls from the second week to the third week [2 nd week： 22.92±1.631 mm Hg（n=5） vs 17.35±0.751 mm Hg（n=5）; 3 rd week： 23.59±1.494 mm Hg vs 17.73±0.592 mm Hg（n=5）], while light time IOP was comparable between groups. The fluctuation levels of IOP in the experimental eyes were 7.21±0.398 mm Hg（n=5）, 9.50±1.017 mm Hg（n=5） and 10.66±0.894 mm Hg（n=5） from the first week to the third week after injection. Comparatively, they were significantly lower in the control eyes, which were 4.69±0.323 mm Hg（n=5）, 2.84±1.122 mm Hg（n=5） and 4.98±0.603 mm Hg（n=5） respectively. However, at the end of 3 wk, the larger fluctuations in IOP in the experimental eyes was not associated with a significant loss of RGCs. CONCLUSION： Microbead occlusion exacerbates diurnal IOP fluctuation in rats. This reported model may serve as a method of investigating the pathological effects of IOP fluctuation. A longer observation period, or repeated injections, may be needed to observe a significant change in RGC density.