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Acute glaucoma is an ocular emergency and sight -threatening disease which is caused by a sudden increase in intraocular ocular pressure (IOP) due to blockage of aqueous humor outflow. Acute glaucoma can result in permanent loss of visual acuity and visual field (VF). Prophylactic or therapeutic medicine is rare for acute glaucoma. In animal studies, a well-established model to investigate this acute IOP spike is by fluid infusion and adjustment of the fluid level to induce high IOP within a few seconds. However, there is no blockage of aqueous outflow and the increase in intraocular pressure is unrealistically rapid. To mimic the IOP profile in human acute glaucoma attack, we propose the use of an ophthalmic viscosurgical device (OVD), Healon 5 (AMO, Santa Ana, CA, USA) which is injected intracamerally to block aqueous outflow. The IOP is allowed to increase naturally inside the globe. We found that Healon 5 can induce an acute elevation in IOP with very similar characteristics to those observed in humans. For example, the IOP profile during the attack, changes in the anterior segment and retinal nerve fibre layer (RNFL) thinning are all consistent with findings in human acute angle closure glaucoma (AACG). We believed that our new model can more accurately reflect acute glaucoma than other animal models. Based on these findings we further tested the neuroprotective effect of Lycium barbarum polysaccharides (LBP) on retinal neurons against an acute rise in IOP (attack) with the new model. L. barbarum is an herb that has been used in Chinese medicine for thousands of years. The fruit of this plant is believed to be good for the health of the eyes. In our study we found that oral administration of LBP preceding an acute glaucoma attack can preserve the visual function of the animals despite the loss of neurons in the retinal ganglion cell layer (RGCL). L. barbarum intake seems to inhibit secondary cell death and progression of the disease. In conclusion, we had successfully established a new acute glaucoma attack animal model by intracameral injection of Healon 5. This model more closely resembles the condition observed in human acute glaucoma. We also found that LBP has a prophylactic neuroprotective effect against an acute glaucoma attack in animals. It can protect the visual function and possibly inhibit secondary cell death. Oral consumption of LBP as a health supplement may provide extra benefit to people who are at high risk of developing acute glaucoma, in addition to the protective effects of LBP against other diseases. / published_or_final_version / Anatomy / Master / Master of Philosophy

Glaucoma is a neurodegenerative disease and one of the major causes of blindness in the world. Secondary degeneration is involved in glaucoma. The retinal ganglion cells (RGCs) which are vulnerable to secondary degeneration in glaucoma are the promising target population for therapeutic intervention. Partial optic nerve transection (PONT) model has been established in the last decade. Primary and secondary degeneration can be separated in different regions of retinas in this model. Therefore, PONT is a good model for the study of mechanisms of secondary degeneration and the drug screening for secondary degeneration. Lycium barbarum (L. barbarum) has been shown to be neuroprotective for cortical neurons in vitro. It has also been shown that L. barbarum could delay RGCs death in a rat ocular hypertension model. In order to further investigate the effects of L. barbarum for RGCs, two models, complete optic nerve transaction (CONT) model and PONT model, were employed in my study. My results showed that the polysaccharide extract from L. barbarum (LBP) could partly prevent RGCs from death in the inferior retinas 4 weeks after PONT whereas it could not reduce the loss of RGCs after CONT. The1,1'-dioctadecyl-3, 3, 3’, 3’-tetramethylindocarbocyanine perchlorate(DiI) labeling of RGCs whose axons were transected showed that the majority of labeled cell bodies existed in the superior retinas. The result meant that more cell bodies in the superior retinas would die from primary degeneration than in the inferior retina after PONT. Therefore my results indicated that LBP protected RGCs which would die from secondary degeneration rather than primary degeneration. The results of Terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL) staining showed that RGCs underwent apoptosis 1 week after PONT. Western-blot analysis demonstrated that oxidative stress was involved in the degeneration of RGCs after PONT. Furthermore, c-Jun N-terminal kinases (JNKs) pathway was activated which was indicated by an increase ofphospho-JNK2/3(p-JNK2/3)and phospho-c-jun(p-c-jun). Our results also revealed that orally feeding of LBP could increase the expression of manganese superoxide dismutase (MnSOD) and insulin growth factor-1 (IGF-1)and decrease the expression of p-JNK2/3 and p-c-jun. The results from optic nerve (ON) study showed that glial cells, including astrocytes and microglias/macrophages, were activated after PONT. Oxidative stress and inflammation were involved in the process. Secondary degeneration of ON was not obvious and LBP exerted no protective effects on the survival of axons in the ON. The multifocal electroretinography (mfERG) study showed that both the functions of inner retinas and outer retinas were damaged after PONT. The results indicated that other cell types or the synapses between different cell types were damaged in addition to RGCs. LBP could improve the function of the whole retinas, including both inner retinas and outer retinas after PONT. In conclusion, our results indicated that LBP protected RGCs from secondary degeneration via inhibiting oxidative stress and the activation of JNK pathway.LBP could also improve the function of both inner retinas and outer retinas after PONT. / published_or_final_version / Anatomy / Doctoral / Doctor of Philosophy

Thesis (M. Phil.)--University of Hong Kong, 2006. / Restricted as requested by author. Restricted access for 1 year 2007--03--28 ; approval pending. Also available online.

Thesis (M. Phil.)--University of Hong Kong, 2006. / Title proper from title frame. Also available in printed format.

This thesis summarize information about Salvia hispanica, known as Chia and Lycium barbarum/chinense, known as Goji, which are plants that provide seeds and fruits used as superfoods. The theoretical part of the thesis is divided into a general description, content substances, health effects, history of use of these plants and an overview of studies with their use. Studies are focused on the study of antioxidant effects, anti-cancer effects, the influence of use superfoods on metabolism and diseases, and studies on the use of these superfoods in common foods. The practical part of the thesis focused on knowledge into superfoods among the population and the rate of their use. The results show that knowledge about superfoods, including chia and Goji, is good, as well as the use of superfoods in the population. Chia and Goji are currently the most widely used superfoods. Less than a third of respondents observe the positive effects of using superfoods. This thesis presents information to potential consumers why they should include superfoods in the diet.

Retinal detachment (RD) is a leading cause of blindness and although final surgical reattachment rate has greatly improved, visual outcome in many macula-off detachments is disappointing, mainly because of photoreceptor cell death. We previously showed that both lutein and Lycium barbarum polysaccharides (LBP) are neuroprotective in a rodent model of ischemia/reperfusion injury. The objective of this study is to investigate lutein and LBP as possible pharmacological adjuncts to surgery. Lutein: Subretinal injections of 1.4% sodium hyaluronate were used to induce RD in Sprague-Dawley rats until their retinae were approximately 70% detached. Daily injections of corn oil (control group) or 0.5mg/kg lutein in corn oil (treatment group) were given intraperitoneally starting 4 hours after RD induction. Animals were euthanized 3 days and 30 days after RD and their retinae were analyzed for photoreceptor apoptosis and cell survival at the outer nuclear layer (ONL) using TUNEL staining and cell counting on retinal sections. Glial fibrillary acidic protein (GFAP) and rhodopsin (RHO) expression were evaluated with immunohistochemistry. Western blotting was done with antibodies against cleaved caspase-3, cleaved caspase-8 and cleaved caspase-9 to delineate lutein’s mechanism of action in the apoptotic cascade. To seek a possible therapeutic time window, the same set of experiment was repeated with treatment commencing 36 hours after RD. When lutein was given 4 hours after RD, there was significantly fewer TUNELpositive cells in ONL 3 days after RD when compared with the vehicle group. Cell counting showed that there were significantly more nuclei in ONL in lutein-treated retinae by day 30. Treatment groups also showed significantly reduced GFAP immunoreactivity and preserved RHO expression. At day 3 after RD, Western blotting showed reduced expression of cleaved caspase-3 and cleaved caspase-8 in the treatment group. No difference was found for cleaved caspase-9. When lutein was given 36 hours after RD similar results were observed. Our results suggest that lutein is a potent neuroprotective agent that can salvage photoreceptors in rats with RD, with a therapeutic window of at least 36 hours. The use of lutein in patients with RD may serve as an adjunct to surgery to improve visual outcomes. LBP: The same RD model was used for the LBP experiment. Phosphate buffered solution (PBS) or LBP in PBS was given orally through a gavage at 1mg/kg and 10mg/kg concentrations. For this experiment, animals were sacrificed 7 days after RD, and only cell counting of the ONL and TUNEL staining were performed. Both sets of results did not produce statistically significant changes with the use of LBP. Our preliminary data for the effect of LBP on retinal detachment shows no significant beneficial effect. / published_or_final_version / Medicine / Master / Master of Research in Medicine

It has been known that light input can affect the emotions of a person. The depressive syndrome Seasonal Affective Disorder (SAD) is an effective example of the power of light in changing the mood of a person. Patients with SAD have recurring depressive episodes that follow seasonal changes, which is due to the changing daylight hours. This phenomenon suggests that there would be receptors in the retina that would not simply be responsible for vision, but also for the regulation of non-visual signals such as emotion. In many animals, projections have been found from the retina to the dorsal raphe nucleus (DRN). This brain region is a serotonergic area and has been found to be involved in the occurrence of depression. As such, the cells in the retina which were found to have projections to the DRN have a high possibility to be involved in emotion regulation. Retinal Ganglion Cells (RGCs) are classified into many types. A specific type known as an alpha cell is suspected to be the DRN-projecting subtype. This study uses Lycium Barbarum Polysaccharide (LBP) as a treatment in protecting the large RGCs from corticosterone (CORT) -induced damage. The aim is to observe if LBP will provide neuroprotection to large sized RGCs damaged by 40mg/kg or 50mg/kg CORT, and hence if LBP can be further investigated as a possible anti-depressant drug. This study observed that although LBP did not reduce large cell deaths, it reduced cell atrophy of the RGCs under high dosage of CORT (50mg/kg). For the same number of cells counted, treatment groups with a high dose CORT injection found more cells over 300μm2 in area than cells under 300μm2. Also, it was found that the temporal quadrants were more sensitive to cell size change than the nasal quadrants, paving way for more in-depth research of the spatial sensitivity to CORT or to LBP. The findings in this study indicate that LBP does indeed have a neuroprotective effect on large RGCs, although this effect is limited and as of yet seems conditional, as this study ignores the effect of CORT and LBP on other large cell properties such as the dendritic field size and the amount of synapses. Further studies are needed to determine the mechanism of the neuroprotective effect of LBP and to determine the exact site of action LBP works on. / published_or_final_version / Anatomy / Master / Master of Medical Sciences

published_or_final_version / abstract / toc / Botany / Master / Master of Philosophy