Role For Bhlh Transcription Factors In Retinal Degeneration And Dysfunction

Bramblett, Jang-Hyeon Cho, Ming-Jer Tsai, and Samuel M. Wu* The basic helix loop helix (bHLH) transcription factors collectively mediate cellular differentiation in almost every type of tissue including the retina (Murre et al. 1989 Jan and Jan 1993 Cepko 1999). Class A factors are ubiquitously expressed throughout mammalian tissue, while the expression of class B factors are cell type specific. These factors have both a DNA binding domain and helix loop helix domain...

Space Flight Environment Induces Degeneration In The Retina Of Rat Neonates

Barnstable* Retinal degenerations can be promoted by many factors including ageing, ischemia, fluctuation in oxygen tension, oxidative stress, and increased intraocular pressure. We present new evidence that the environment encountered in space shuttle flight can also disrupt normal retinal development and mimic stimuli that induce retinal degenerations on earth. There is experimental evidence linking anomalies in visual perception with space flights since the...

The Neuroretina

Egwuagu, Cheng-Hong Yu, Rashid M. Mahdi, Marie Mameza, Chikezie Eseonu, Hiroshi Takase, and Samuel Ebong* The vertebrate retina is comprised of a collection of highly specialized cell types, with each subtype playing unique roles and functions in the reception, transduction and conversion of incident light rays into visual images. The photo-transduction mechanism is extremely sensitive and minute alterations in the relative abundance of any retinal cell type can severely compromise...

Introduction

For many years, blue light damage associated with retinal pigment epithelial (RPE) cell lipofuscin (LF) has been implicated in the cause of age-related macular degeneration (AMD) (Young, 1988 Winkler et al., 1999 Bressler et al., 2000) and other retinal degenerative diseases, such as Stargardt's disease, (Lopez et al., 1990 Birnbach et al., 1994), Best's macular dystrophy (Weingeist et al., 1982) and cone-rod dystrophy (Rabb et al., 1986). A2E and isomers, pyridinium bis-retinoid compounds and...

Gene Delivery To The Retina Using Lentiviral Vectors

Lee2'3, David V Schaffer2'4, and John G. Flannery1'2 The delivery of foreign DNA to the retina has proven to be a valuable tool for investigations of retinal disease, development, and complex cellular interactions. To achieve efficient and stable retinal gene expression with minimal unwanted side effects, viral vectors derived from AAV (adeno-associated virus) and LV (lentivirus) remain the vehicles of choice. LV vectors have gained recent attention in CNS gene...

For Assessing Mouse Vision

Yumiko Umino, Bridget Frio, Maryam Abbasi, and Robert Barlow The retina is an important model for studies of neurodegeneration. More than 100 gene mutations are known to cause retinal degeneration (Chader, 2002 Pacione et al., 2003 Rattner et al., 1999). Studies of retinal degeneration in mammals have focused on mouse because of the knowledge of its genome together with the ease of its breeding and husbandry (Naash et al., 2004 Olsson et al., 1992 Pinto et al., 2004). Assessment of the...

C

Immunofluorescent images of retinas stained with antibodies to S-opsin (A and C), or M-opsin (B and D), from non-transgenic (A and B), and LIF expressing transgenic mice (C and D). Photoreceptor outer segments are oriented to the top of each panel. Figure 22.2. Semi-quantitative RT-PCR analysis of Nr2E3, and Tr 32 expression from non-transgenic mice (NTG) and LIF expressing transgenic mice (736). Samples were run for either 24 or 35 cycles. were unable to detect either cone opsin...

References

C., Xie, H., Clarke, S., O'Brien, P. J., and Fung, B. K. K. (1992). In vivo differential preny-lation of retinal cyclic GMP phosphodiesterase catalytic subunits. J. Biol. Chem. 267 687-690. Baehr, W., Devlin, M. J., and Applebury, M. L. (1979). Isolation and characterization of cGMP phosphodiesterase from bovine rod outer segments. J. Biol. Chem. 254 1669-11677. Beavo, J. A., Conti, M., and Heaslip, R. J. (1994). Multiple cyclic nucleotide phosphodiesterases. Mol....

Effect of FBS and PEDF on VEGF Synthesis in hRPE Cells

Figure 71.3 shows that FBS stimulates 14-C-methionine-VEGF in dose dependent manner. Figure 71.4 shows that PEDF (0.1 mg ml) inhibits FBS (10 ) stimulated 14-C- Control 10 FBS 1 ng ml PEDF 10 ng ml PEDF 100 ng ml PEDF Figure 71.1. Effect of PEDF on FBS stimulated hRPE cell proliferation (*, **, *** p < 0.05 when compared with each other. Control 10 FBS 1 ng ml PEDF 10 ng ml PEDF 100 ng ml PEDF Figure 71.1. Effect of PEDF on FBS stimulated hRPE cell proliferation (*, **, *** p < 0.05 when...

Avb5 Signaling Via Focal Adhesion Kinase Activates Mertk During Rpe Phagocytosis In Vivo And In Vitro

Previous studies have shown that phosphorylation of FAK at tyrosine residue 861 promotes direct binding of FAK to the cytoplasmic face of avb5 integrin receptors (Eliceiri et al., 2002). In our studies, we observed increased levels of FAK in avb5 protein complexes isolated by immunoprecipitation from RPE-J cells during the early POS binding phase but loss of FAK from the integrin complex during the later POS internalization phase (Finnemann, 2003). Residence of FAK in the complex correlated...

Robert S Molday Seelochan Beharry Jinhi Ahn and Ming Zhong

ABCA4, also known as ABCR or the rim protein, is a member of the ABCA subfamily of ATP binding cassette transporters (Allikmets et al., 1997b Azarian and Travis, 1997 Illing et al., 1997). It is organized into two tandem arranged halves with each half consisting of a transmembrane segment followed by a large extracellular domain, a multi-spanning membrane domain and a cytoplasmic nucleotide binding domain (Figure 64.1) (Bungert et al., 2001). ABCA4 is localized along the rims and incisures of...

Neural Plasticity Revealed By Lightinduced Photoreceptor Lesions

Marc, Carl B. Watt, Dana K. Vaughan, and Daniel T. Organisciak* The retina has long been assumed to remain in stasis after photoreceptor degeneration effectively deafferents the neural retina (Zrenner, 2002). However, a growing literature reveals the more insidious details of retinal degeneration and evidence of early plasticity. Retinal degenerations typically undergo three phases. Early changes observed in phase one are triggered by photoreceptor stress and include...

Altered Rhythm Of Photoreceptor Outer Segment Phagocytosis In p5 Integrin Knockout Mice

Finnemann1,2* In the retina photoreceptor and retinal pigment epithelial cells (RPE cells) are in close contact. The outer segment portions of photoreceptors consist of stacked membranous disks containing the phototransduction machinery. These disks are permanently produced thereby lengthening outer segments. To maintain constant outer segment length photoreceptors eliminate their most aged tips by daily shedding (Young, 1967). RPE cells form a polarized...

Retinal Damage Caused By Photodynamic Therapy Can Be Reduced Using Bdnf

Paskowitz, George C. Nune, Douglas Yasumura, Haidong Yang, Michael T. Matthes, Marco A. Zarbin, and Matthew M. LaVail* Age related macular degeneration (AMD) is the leading cause of blindness among the elderly in the United States (Klein et al., 1992 Klein et al., 2002), and choroidal neovascularization (CNV) accounts for the majority of severe vision loss (Ferris et al., 1984). The current standard treatment for CNV is verteporfin photodynamic therapy (PDT) (Landy...

Controlling Vascular Endothelial Growth Factor Therapies For Ocular Diseases Associated With Neovascularization

Elizabeth Rakoczy2 Vascular endothelial growth factor (VEGF) is a potent stimulator of angiogenesis and is essential for normal embryonic development and many physiological events that require the growth of new blood vessels. Abnormal expression of endogenous VEGF can lead to ocular diseases including age related macular degeneration (Ohno-Matsui et al., 2001) and diabetic retinopathy (Aiello et al., 1994 Boulton et al., 1998), which are the two leading causes of...

Mouse Retinas

Reza Ghassemifar1'2'*, Chooi-May Lai2, and P. Elizabeth Rakoczy2 Tight junctions (TJ) are specialized multiprotein complexes which act to seal the intercellular space and thereby generate a permeability barrier required for transport processes (Matter and Balda, 1999). In addition, by regulation of the TJs, the paracellular pathway may be opened for selective transport of molecules, ions (Madara et al., 1992) and neutrophils (Huber et al., 2000). Thus far several interacting constituents...

NN2 QpMrQpOzT XXX jPQQH aM4MBaa

NH2 -Q fD-( ) PCZ2 '-XXX X) -i EST 0-Q jT OOB D 852-910 Figure 48.1. Cartoon showing the domains of the different harmonin isoforms and the regions recognized by the three different antibodies (H1, H2 & H3). We immunodetected myosin Vila in mouse and human retinas by immunofluorescence and immunoelectron microscopy. In the RPE cells, myosin Vila is found in the apical processes (Fig. 48.2A, B). To elucidate more precisely the distribution of myosin Vila in the RPE cells and the organelles...

Factors Underlying Circadian Dependent Susceptibility To Light Induced Retinal Damage

Ruby Grewal1, Daniel Organisciak2, and Paul Wong1,3 Retinal cell loss in diseases such as Retinitis Pigmentosa occurs through an apoptotic process.1 The mechanism of this cell loss is not completely understood. Models that allow for the study of conditions in which the retina is susceptible or resistant to retinal damage help to elucidate the mechanism underlying the cell death. One model that is used to study retinal cell loss is the light induced retinal degeneration (LIRD) model.2 Intense...