An experimental study of lateral displacement of ganglion cells (GCs) from foveal cones in six human retinas is reported. At 406-675 microm in length, as measured in radially oriented cross-sections, Henle fibers are substantially longer than previously reported. However, a new theoretical model indicates that the discrepancies in these reports are mainly due to meridional differences. The model takes into account the effects of optical degradation and peripheral ON/OFF asymmetry and predicts a central GC:cone ratio of 2.24:1. It provides estimates of cumulative counts and GC receptive field density at 0 degrees -30 degrees along the principal meridians of the visual field.

Cilia are complex organelles involved in sensory perception and fluid or cell movement. They are constructed through a highly conserved process called intraflagellar transport (IFT). Mutations in IFT genes, such as Tg737, result in severe developmental defects and disease. In the case of the Tg737orpk mutants, these pathological alterations include cystic kidney disease, biliary and pancreatic duct abnormalities, skeletal patterning defects, and hydrocephalus. Here, we explore the connection between cilia dysfunction and the development of hydrocephalus by using the Tg737orpk mutants. Our analysis indicates that cilia on cells of the brain ventricles of Tg737orpk mutant mice are severely malformed. On the ependymal cells, these defects lead to disorganized beating and impaired cerebrospinal fluid (CSF) movement. However, the loss of the cilia beat and CSF flow is not the initiating factor, as the pathology is present prior to the development of motile cilia on these cells and CSF flow is not impaired at early stages of the disease. Rather, our results suggest that loss of cilia leads to altered function of the choroid plexus epithelum, as evidenced by elevated intracellular cAMP levels and increased chloride concentration in the CSF. These data suggest that cilia function is necessary for regulating ion transport and CSF production, as well as for CSF flow through the ventricles.

To determine the distributions of basal laminar and basal linear deposits in Bruch membrane (BM) with respect to age and early age-related maculopathy (ARM). Methods: The foveas of 41 human eyes (Ͻ60 years [n = 9]; Ն60 years [n = 32]), preserved no later than 3.5 hours post mortem, were examined using light and electron microscopy. Ten eyes met histopathologic criteria of the Alabama Age-related Macular Degeneration Grading System for early ARM. We calculated the specificity, sensitivity, and odds ratios for the association of basal laminar and basal linear deposits with early ARM. Results: Both deposits occurred only in eyes older than 60 years. The highest specificities and sensitivities for early ARM were attained for eyes that had basal linear deposits or large (Ͼ125 µm) drusen, followed by eyes with any quantity of basal laminar deposits that also contained membranous debris. Eyes with ARM were 24 times more likely than age-matched control eyes to have basal linear deposits or large drusen (P = .002). Conclusions: Basal linear deposits and large drusen with membranous contents constitute different morphologic forms of the same ARM-associated lesion and may be significant for progression to late ARM.

Hyperthermia can be produced by near-infrared laser irradiation of gold nanoparticles present in tumors and thus induce tumor cell killing via a bystander effect. To be clinically relevant, however, several problems still need to be resolved. In particular, selective delivery and physical targeting of gold nanoparticles to tumor cells are necessary to improve therapeutic selectivity. Considerable progress has been made with respect to retargeting adenoviral vectors for cancer gene therapy. We therefore hypothesized that covalent coupling of gold nanoparticles to retargeted adenoviral vectors would allow selective delivery of the nanoparticles to tumor cells, thus feasibilizing hyperthermia and gene therapy as a combinatorial therapeutic approach. For this, sulfo-N-hydroxysuccinimide labeled gold nanoparticles were reacted to adenoviral vectors encoding a luciferase reporter gene driven by the cytomegalovirus promoter (AdCMVLuc). We herein demonstrate that covalent coupling could be achieved, while retaining virus infectivity and ability to retarget tumor-associated antigens. These results indicate the possibility of using adenoviral vectors as carriers for gold nanoparticles.

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The data suggest that the predilection of a extremely thin sublayer of inner Bruch's membrane for accumulating lipid particles may eventually lead to a confluent lipid wall capable of isolating the retina from its blood supply. If these lipids originate in the retinal pigment epithelium, then they are unlikely to have passed through the basal lamina in this form. The age-related increase in lipid particles corresponds with an age-related increase in hydraulic resistance determined in excised Bruch's membrane/choroid by others. QFDE will be useful for future modeling studies of Bruch's membrane transport and to identify those moieties responsible for deleterious age-related transport changes in Bruch's membrane.

SUMMARY1. The psychophysical spectral sensitivity of cats was assessed using a two-choice visual discrimination task by determining increment thresholds and critical flicker frequency on white and chromatic backgrounds.2. For large increments, on 0 0, 0 3 and 3 0 cd/M2 white backgrounds, the cats were most sensitive to 497 nm indicating that these backgrounds are scotopic. On 30 and 300 cd/M2 white backgrounds, the cats were most sensitive to about 454 and 561 nm indicating that these backgrounds are photopic. Sensitivity to intermediate wave-lengths indicated independent action of 'blue' and 'green' cones.3. For large increments, thresholds on photopic yellow and magenta backgrounds indicated the additive influence of 'blue' and 'green' cones.4. Spectral sensitivity functions obtained with a critical flicker frequency criterion of 10 Hz on a 30 cd/M2 white background reflected only the activity of the 'green' cone while at 20 Hz the function reflected an additive contribution of both 'blue' and 'green' cones.5. For small increments, on a 30 cd/M2 white or 96 cd/M2 orange background, sensitivity reflected only the activity of the 'green' cone.6. The cat's photopic spectral sensitivity is influenced by the psychophysical test upon which it is based in a manner that is similar to what has been found for other vertebrates. No evidence was found for a 500 nm mechanism active at photopic levels.

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