Thesis (Ph. D.)--University of Washington, 1997. / Vita. Includes bibliographical references (leaves [92]-96).

Wang Zhi-Jun. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1997. / Includes bibliographical references (leaves 54-63). / ABSTRACT --- p.VI / Chapter I. --- INTRODUCTION --- p.1 / Chapter A. --- Literature review --- p.1 / Chapter 1. --- Retinal iron toxicity --- p.2 / Clinical siderotic retinopathy --- p.2 / Experimental siderotic retinopathy --- p.4 / Free radical involvement in siderotic retinopathy --- p.5 / Chapter 2. --- Experimental photic retinopathy in rats --- p.8 / Morphologic features --- p.8 / Free radical involvement in photic retinopathy --- p.9 / Chapter 3. --- Mechanisms of cell death --- p.9 / Necrosis --- p.10 / Apoptosis --- p.10 / Chapter B. --- Statement of the problems --- p.15 / Chapter II. --- MATERIALS AND METHODS --- p.17 / Chapter A. --- Siderotic retinopathy model --- p.17 / Animals --- p.17 / Reagents and equipment --- p.18 / Surgical procedures --- p.18 / Chapter B. --- Histochemical methods --- p.18 / Reagents and equipment --- p.19 / Paraffin sections --- p.19 / H&E staining --- p.19 / TUNEL technique --- p.20 / Schmeltzer's iron staining --- p.21 / Chinoy's ascorbic acid staining --- p.21 / Chapter C. --- Biochemical methods --- p.21 / Reagents and equipment --- p.22 / DNA gel electrophoresis --- p.22 / Analysis of ascorbic acid and uric acid --- p.23 / Chapter III. --- RESULTS --- p.24 / Chapter A. --- Observations in rats --- p.24 / Morphologic changes after H&E staining --- p.24 / Visualization of apoptosis by TUNEL technique --- p.25 / Internucleosomal DNA fragmentation --- p.26 / Negative staining of iron in the ONL --- p.27 / Positive staining of ascorbic acid in the ONL --- p.27 / Chapter B. --- Observations in rabbits --- p.27 / Positive staining of ascorbic acid in all retinal layers --- p.27 / Apoptosis occurred in all retinal layers --- p.28 / Changes of ascorbic acid and uric acid after iron implantatio --- p.28 / Chapter IV. --- DISCUSSION --- p.48 / Chapter V. --- CONCLUSION --- p.53 / References --- p.54

Thesis (Ph. D.)--University of Washington, 2003. / Vita. Includes bibliographical references (leaves 80-91).

Thesis (Ph. D.)--University of Washington, 2007. / Vita. Includes bibliographical references (leaves 126-138).

Thesis (Ph.D.)--University of Alabama at Birmingham, 2009. / Title from first page of PDF file (viewed on June 10, 2009). Includes bibliographical references.

Thesis (Ph. D.)--University of Washington, 1996. / Vita. Includes bibliographical references (leaves [145]-174).

Thesis (Ph. D.)--University of Alabama at Birmingham, 2008. / Title from first page of PDF file (viewed Feb. 12, 2009). Includes bibliographical references (p. 136-146).

by Pik-ying Ng. / Bibliography: leaves 106-117 / Thesis (M.Phil.)--Chinese University of Hong Kong, 1983

Thesis (Ph. D.)--University of Washington, 2007. / Vita. Includes bibliographical references (leaves 107-117).

Retinitis Pigmentosa (RP) is an inherited photoreceptor degenerative disease that leads to blindness and affects about 1 in 4000 people worldwide. The disease is predominantly caused by mutations in genes expressed exclusively in the night active rod photoreceptors; however, blindness results from the secondary loss of the day active cone photoreceptors, the mechanism of which remains elusive. Here, we show that the mammalian target of rapamycin complex 1 (mTORC1) is required to delay the progression of cone death during disease and that constitutive activation of mTORC1 is sufficient to maintain cone function and promote cone survival in RP. Activation of mTORC1 increased expression of genes that promote glucose uptake, retention and utilization, leading to increased NADPH levels; a key metabolite for cones. This protective effect was conserved in two mouse models of RP, indicating that the secondary loss of cones can be delayed by an approach that is independent of the primary mutation in rods. However, since mTORC1 is a negative regulator of autophagy, its constitutive activation led to an unwarranted secondary effect of shortage of amino acids due to incomplete digestion of autophagic cargo, which reduces the efficiency of cone survival over time. Moderate activation of mTORC1, which promotes expression of glycolytic genes, as well as maintains autophagy, provided more sustained cone survival. Together, our work addresses a long-standing question of non-autonomous cone death in RP and presents a novel, mutation-independent approach to extend vision in a disease that remains incurable.