Yes / We used triple silent substitution stimuli to characterize human S-cone electroretinograms (ERGs) in normal trichromats. Short-wavelength-cone (S-cone) ERGs were found to have different morphological features and temporal frequency response characteristics compared to ERGs derived from L-cones, M-cones, and rod photoreceptors in normal participants. Furthermore, in two cases of retinal pathology, blue cone monochromatism (BCM) and enhanced S-cone syndrome (ESCS), S-cone ERGs elicited by our stimuli were preserved and enhanced, respectively. The results from both normal and pathological retinae demonstrate that triple silent substitution stimuli can be used to generate ERGs that provide an assay of human S-cone function. / Deutsche Forschungsgemeinschaft (DFG) (KR1317/13-1); Bundesministerium für Bildung und Forschung (BMBF) (01DN14009)

Diss. (sammanfattning) Stockholm : Karol. inst., 2004. / Härtill 5 uppsatser.

After over a decade of its discovery, the Electroretinogram (ERG) still remains the objective tool that is conventionally used in assessment of retinal function in health and disease. Although there is ongoing research in developing ERG recording techniques, interpretation and clinical applications, there is still a limited understanding on how each photoreceptor class contribute to the ERG waveform and their role and/or susceptibilities in various retinal diseases still remains unclear. Another limitation with currently used conventional testing protocols in a clinical setting is the requirement of an adaptation period which is time consuming. Furthermore, the ERG responses derived in this manner are recorded under different stimulus conditions, thus, making comparison of these signals difficult. To address these issues and develop a new testing method, we employed silent substitution paradigm in obtaining cone- and rod- isolating ERGs using sine- and square- wave temporal profiles. The ERGs achieved in this manner were shown to be photoreceptor-selective. Furthermore, these responses did not only provide the functional index of photoreceptors but their contributions to their successive postreceptoral pathways. We believe that the substitution stimuli used in this thesis could be a valuable tool in functional assessment of individual photoreceptor classes in normal and pathological conditions. Furthermore, we speculate that this method of cone/rod activity isolation could possibly be used in developing faster and efficient photoreceptor-selective testing protocols without the need of adaptation. / Bradford School of Optometry and Vision Sciences scholarship

Battlefield retinal laser injury is an infrequent but potentially devastating cause of irreversible blindness. Resultant laser-induced photoreceptor death may occur by necrosis or apoptosis, the latter which is a form of programmed cell death that may be physiological or pathological. Though necrosis cannot be prevented, apoptosis may be inhibited under certain conditions. Therefore, following retinal laser injury, specific treatment aims to target apoptotic photoreceptors and may take the form of neuroprotection or cell replacement. The primary aim of this thesis was to construct an in vivo model in which to observe the effects of retinal laser exposure on cone photoreceptor apoptosis. Current methodology to determine the effects involves histological techniques and is therefore limited to being cross-sectional. An in vivo model would permit longitudinal study to observe the cone response to injury using clinically relevant applications, including fundus autofluorescence imaging. Such a construct would enable more sensitive evaluation of new therapies which would be of direct translational relevance. The secondary aim was to investigate potential therapeutic options for retinal laser injury by pharmacological means in the form of CNTF or cell transplantation. To identify the possible molecular signals involved in neurotrophic factor-induced photoreceptor cell survival, apoptotic gene expression was investigated focusing on those genes modulated by the CNTF pathway.

The childhood eye cancer retinoblastoma originates from the retina and its development is initiated while the foetus is in the uterus. Retinoblastoma has a reported incidence of 1 in 15-18 000 live births, and approximately 90% of all patients are diagnosed before the age of 5. The occurrence of retinoblastoma is usually detected by the parents and the most frequent symptoms are leukocoria (white pupillary reflex), strabismus (squinting) or if the child complains of visual problems. Retinoblastoma is diagnosed by examination under anaesthesia and documentation by RetCam. It is treated with various cytostatic agents, or by laser. If the treatment is unsuccessful, or there is a risk that the tumour cells will spread and form metastases, the eye is removed. Previous studies have indicated that the cell type from which the tumour arises, the cell-of-origin, may be the cone photoreceptors and/or their immediate interneuron, the horizontal cells. Determining the cell-of-origin for retinoblastoma is an important goal, however, understanding the molecular mechanisms that distinguish the photoreceptors and the horizontal cells from the other retinal cells may prove just as important for understanding this disease. The aim of my project has been to develop, optimise and validate methods to label, map and target expression to photoreceptors and horizontal cells in the chicken embryonic retina. We have successfully established several methods that test the expression pattern of conserved, regulatory DNA sequences, and have performed short- and long-term expression of various genes that have been reported to be involved in cell cycle regulation and cell fate determination. One of my most important findings was that a region from the RXRγ gene allowed us to specifically target the photoreceptors and horizontal cells. Our previous knowledge, together with the newly established tools, puts us an important step closer towards understanding the development and behaviour of the retinal photoreceptors and horizontal cells, however, further studies are of course needed.

Phototransduction is a well characterized system for study of G protein coupled receptor (GPCR) signaling. The GPCR rhodopsin couples to the heterotrimeric G protein transducin. Light-stimulated activation of transducin in turn activates phosphodiesterase (PDE), leading to closure to cGMP-gated channels and inhibition of glutamate release. Rod and cone photoreceptors are highly polarized neurons consisting of the outer segment (OS) where phototransduction biochemistry occurs, the inner segment containing mitochondria and other organelles, the nuclear layer, an axon, and a glutamatergic synapse. Upon illumination, activated G protein transducin redistributes from the rod OS (where it is localized in the dark) to the inner compartments of the cell. Interestingly, cone transducin does not translocate in light. Opposite to this, visual arrestin migrates from the inner compartments to the OS, where it binds to rhodopsin. Previous reports from other groups and our lab argue for either an active or passive mechanism for transducin and arrestin redistribution. Our lab has shown that arrestin migration occurs by diffusion which is restricted by molecular sinks (Nair et al, 2005b). The focus of my dissertation was to unravel the molecular mechanism of rod transducin translocation. Specifically, I found energy (ATP) was not required for transducin movement within photoreceptors. Also, I found that the disc membranes of the rod outer segments as well as protein-protein interactions with retinal guanylate cyclase serve to restrict transducin diffusion through the cell. In addition, I used the insights gained from these studies of transducin to re-examine the relationship of other G proteins' subcellular localization and signal transduction. Ultimately, I found that most G proteins do not undergo subunit dissociation under physiological activating conditions.

M. Tech. Agriculture. / Investigates the effect of photo-selective nets on plant growth parameters (plant height, leaf area, leaf chlorophyll, stem diameter, flowering intensity, and fruit settings), pest and disease incidence, and yield (number of fruits per plant) in three selected cultivars.Secondly, to investigate the effect of shading on fruit quality parameters (fruit mass, firmness, colour, soluble solids content, and titratable acidity) and health promoting compounds (ascorbic acid, lycopene content, β-carotene, total phenols and flavonoids, and antioxidant scavenging activity) in three selected tomato cultivars.

The role of the retinal pigment epithelial cells on the viability and renewal of photoreceptors has been well demonstrated in the Royal College of Surgeons (RCS) strain of rat. These rats are characterized by an inherited time-dependent degeneration of their photoreceptors. This degeneration is apparently due to the inability of the retinal pigment epithelial cells to adequately ingest fragments of photoreceptor membrane that are shed during the course of photoreceptor membrane renewal. The buildup of photoreceptor material in the interphotoreceptor space ultimately leads to the degeneration of photoreceptors in these animals. With regard to the pigment epithelial cells, neither the mechanism mediating the ingestion process in normal rats nor the nature of the defect of this process in RCS rats is understood.It is the goal of this proposed research to assay for the presence of phospholipase C in retinal pigment epithelial (RPE) cells and to determine possible modulators of the enzyme in an attempt to associate this with the process of phagocytosis. / Department of Biology

Thesis (Ph.D.). / Written for the Dept. of Electrical & Computer Engineering. Title from title page of PDF (viewed 2009/06/08). Includes bibliographical references.

Thesis (Ph. D.) -- University of Texas Southwestern Medical Center at Dallas, 2004. / Vita. Bibliography: 154-160.