A hallmark of retinal diseases is degeneration of neural cells, leading to subsequent vision loss. For such diseases, replenishment of functional neural cells may be an optimal therapy. Unlike humans, the adult red-spotted newt, Notophthalmus viridescens, possesses the remarkable ability to regenerate a complete retina following its removal or injury. The purpose of this study was to develop a reproducible model of retinal damage and regeneration in the newt to understand the process of retinal regeneration. Intense light, shown in other organisms to be a relevant model of visual cell loss, was tested in the newt and resulted in variable loss of retinal function, correlating with the appearance of apoptotic cells. Due to the variability of damage observed, surgical removal of the retina was used to complement the light-damage model. A novel and non-invasive protocol using full-field electroretinography was developed to assess retinal function in vivo following damage. Measures of retinal function with the electroretinogram protocol successfully showed that photoreceptor function is initially lost and subsequently restored during regeneration. These results enhance our understanding of retinal regeneration in the adult newt and serve as a starting point for further studies aimed at determining the molecular mechanisms involved in the regeneration process.

Aged-related macular degeneration (AMD) is a common eye condition among people older than 65 years and is a leading cause of vision loss. It gradually destroys the macula, the part of the eye that provides sharp, central vision needed for seeing objects clearly. This study aims to test the hypothesis that the morphology of retina pigment epithelium, a key site of AMD pathology, can reflect the various stresses aging and AMD progression impose. We first identify and separate the young and old age group for mouse eyes. Then we classify, the mouse eyes using two genotypes (C57BL/6L, RD10), and two age group (young, old).We show that without dimensional reduction, the cell area and shape measures do not provide good classification of the mouse eyes. But with the dimension reduction at the eye level, the cell area and shape measures provide excellent classification for mouse genotype and age.

ABSTRACT Purpose: The primary aim of the study (i.e. Chapter 3) was to compare the magnitude of retinal vascular reactivity in arterioles of varying diameter in healthy, young subjects. The secondary aims were to determine: a) if there are any order effects in terms of provoking vasoconstriction or vasodilation first; and b) the repeatability of the vascular reactivity measurements. An additional aim (i.e. Chapter 4) was to determine the effect of healthy aging on the relationship between retinal vascular reactivity and vessel diameter. Method: The sample comprised 10 healthy, young subjects (mean age 26.5 years, SD 4.04) and 7 healthy, older subjects (mean age 55.43 years, SD 5.41). Each subject from the young age group attended for three sessions. The first session was used to determine eligibility and select hemodynamic measurement sites. At sessions 2 and 3, O2 and CO2 were sequentially administered to the subjects using a face mask and sequential re-breathing circuit (to maintain standardized hyperoxia and hypercapnia). The order of vasoconstriction and vasodilation was varied across sessions 2 and 3. The design of the protocol was simplified for the subjects from the older age group. Each subject from the older group attended for one visit. O2 and CO2 were administered to the subjects using a face mask and sequential re-breathing circuit. The order of gas provocation was varied among the subjects (i.e. hyperoxia or hypercapnia first). For both groups, measurements of vessel diameter, centerline blood velocity and derived blood flow were acquired at each condition (i.e. baseline, during stabilized vasoconstriction, vasodilation, and recovery) at two discrete measurement sites along the supero-temporal arteriole. Results: The results of the repeated measures ANOVA showed a significant difference between the narrow and wide measurement sites for the younger group for flow (p≤ 0.0003) and a significant influence of inspired gas provocation on flow for both protocols (p<0.0001). In addition, the interaction of measurement site and inspired gas provocation was significant (p<0.0001). The magnitude of retinal vascular reactivity showed a significantly greater blood flow response for the wide measurement site (p<0.0001). O2 provocation resulted in vasoconstriction that was still present up to 10 minutes after cessation of the stimulus (order effect of O2; p≤0.046). No such order effect was apparent for CO2 provocation (order effect of CO2; p=0.352). The group mean blood flow Coefficient of Repeatability (COR) for the narrow measurement site was 0.74 µl/min (relative to group mean flow of 4.85 µl/min ± SD 1.31) and for the wide measurement site was 1.49 µl/min (relative to group mean flow of 11.29 µl/min ± SD 3.55). There was no difference between the young and the older age groups in retinal vascular reactivity for both the narrow (two-tailed Student t-test, p=0.8692) and wide (two-tailed Student t-test, p=0.2795) measurement sites. Conclusion: This study demonstrated that the magnitude of retinal vascular reactivity was greater for arteriolar measurement sites with wider baseline vessel diameters. In addition, it demonstrated that hyperoxic provocation resulted in a persistent vasoconstriction up to 10 minutes after cessation of the stimulus. The study demonstrated that the repeatability of retinal blood flow measurements in absolute terms is lower for smaller diameter vessels. Finally, this study also suggests that age does not affect the relationship between retinal vascular reactivity and vessel diameter.

Thesis (M. Phil.)--University of Hong Kong, 1982.

A polarization sensitive optical coherence tomography (PS-OCT) instrument is presented for the study of glaucoma. Glaucoma is the second leading cause of blindness worldwide and causes irreversible damage to the retina. This PS-OCT system was built to perform retinal imaging with a swept source laser providing a 28 kHz A-scan repetition rate. Thickness, phase retardation, birefringence and reflectance index measurements were taken from the primate eyes on a weekly or semi-weekly basis through the course of a 30 week study. Statistical analysis of these measurements indicates that the reflectance index is the earliest measured indicator of glaucomatous changes and a potential marker for early glaucoma diagnosis. / text

Tumor stroma is known to affect tumor growth and metastasis. Inhibiting PDGF signaling, with the goal of depleting PDGFR&beta;+ stromal cells, is a putative therapeutic approach in this context. PDGFR&beta; is widely accepted as a pericyte marker and targeting PDGF signaling primarily affects pericytes. Pericyte-endothelial cell interactions modulate angiogenesis and vascular stability in developmental and pathological contexts. Owing to this, pericytes are speculated to be important regulators of tumor growth and metastasis, although their role is not clear.

published_or_final_version / Anatomy / Master / Master of Philosophy

published_or_final_version / Anatomy / Master / Master of Philosophy

The retina is able to adjust its signaling over a wide range of light levels. A functional result of this is increased visual acuity at brighter luminance levels, such as during the day, due to changes in the organization of retinal receptive fields. This process is commonly referred to as light adaptation. These organizational changes have been shown to occur at the level of the ganglion cells, the output neurons of the retina, which have shifts in their excitatory center-inhibitory surround receptive fields that increase their sensitivity to small stimuli. Recent work supports the idea that light-adapted changes in ganglion cell spatial sensitivity are due in part to inner retinal signaling changes, possibly including changes to inhibition onto bipolar cells, the interneurons at the center of retinal signal processing. However, it is unknown how inhibition to the bipolar cells changes with light adaptation, how any changes affect the light signal or what mediates the changes to the bipolar cells that have been suggested by previous reports. To determine how light adaptation affects bipolar cell inhibition, the inhibitory inputs to OFF bipolar cells were measured. OFF bipolar cells, which respond to the offset of light, in particular may be involved in retinal adaptation as they bridge dim- and bright-light retinal pathways. Their inputs were compared between dark- and light-adapted conditions to determine how any inhibitory changes affects their output onto downstream ganglion cells. We found that there was a compensatory switch from primarily glycinergic-mediated inhibition to OFF bipolar cells in the dark to primarily GABAergic-mediated inhibition in the light. Since glycinergic and GABAergic inhibition perform very different roles and are mediated by morphologically different cells, it is likely this switch underlies a change in the spatial distribution of inhibition to these cells. We found that the spatial inhibitory input to OFF bipolar cells became significantly smaller and narrower with light adaptation, translating to smaller inhibitory surrounds of the OFF bipolar cell receptive fields. Through a model, our data suggested that the OFF bipolar cell output to downstream ganglion cells was stronger in the light, due to the narrowing and reduction in the spatial input, to small light stimuli. This would effectively be one way the retina could use to increase visual acuity. Additionally, we found that the inhibitory changes to OFF bipolar cells with light-adaptation are partially mediated by dopamine D1 receptor signaling. Dopamine is released in the light and has been shown to be an important modulator of retinal light-adaptation. However, there are likely other factors involved in mediating inhibitory changes to OFF bipolar cells. Through these studies, we show that light adaptation heavily influences inner retina inhibition and likely plays a prominent role in determining and shaping light signals under different ambient light conditions which may ultimately be one mechanism for increasing visual sensitivity and acuity.

No description available.