Subretinal hyperreflective material in regions of atrophy and fibrosis in eyes with neovascular age-related macular degeneration.

Background: Subretinal hyperreflective material (SHRM) is a significant biomarker for poor visual outcomes in neovascular age-related macular degeneration (nAMD); however, its relationship with fibrosis and atrophy is not well understood. This study aims to evaluate the relationship between SHRM, atrophy, and fibrosis in eyes receiving antivascular endothelial growth factor therapy for nAMD.

Methods: Post-hoc analysis of the 65 patients enrolled in the SEVEN-UP study, a multicenter cross-sectional study of patients originally enrolled in the ANCHOR and MARINA trials of ranibizumab.

Role of the superior salivatory nucleus in parasympathetic control of choroidal blood flow and in maintenance of retinal health.

The vasodilatory pterygopalatine ganglion (PPG) innervation of the choroid is under the control of preganglionic input from the superior salivatory nucleus (SSN), the parasympathetic portion of the facial motor nucleus. We sought to confirm that choroidal SSN drives a choroid-wide vasodilation and determine if such control is important for retinal health. To the former end, we found, using transscleral laser Doppler flowmetry, that electrical activation of choroidal SSN significantly increased choroidal blood flow (ChBF), at a variety of choroidal sites that included more posterior as well as more anterior ones.

Effect of the Decrease in Luminance Noise Range on Color Discrimination of Dichromats and Trichromats.

Color vision assessment can be done using pseudoisochromatic stimuli, which has a luminance noise to eliminate brightness differences between the target and background of the stimulus. It is not clear the influence of the luminance noise on color discrimination. We investigated the effect of change in the luminance noise limits on color discrimination.

Defective Choroidal Blood Flow Baroregulation and Retinal Dysfunction and Pathology Following Sympathetic Denervation of Choroid.

Purpose: We sought to determine if sympathetic denervation of choroid impairs choroidal blood flow (ChBF) regulation and harms retina.

Methods: Rats received bilateral superior cervical ganglionectomy (SCGx), which depleted choroid of sympathetic but not parasympathetic innervation. The flash-evoked scotopic ERG and visual acuity were measured 2 to 3 months after SCGx, and vasoconstrictive ChBF baroregulation during high systemic arterial blood pressure (ABP) induced by LNAME was assessed by laser Doppler flowmetry (LDF).

Neural control of choroidal blood flow.

The choroid is richly innervated by parasympathetic, sympathetic and trigeminal sensory nerve fibers that regulate choroidal blood flow in birds and mammals, and presumably other vertebrate classes as well. The parasympathetic innervation has been shown to vasodilate and increase choroidal blood flow, the sympathetic input has been shown to vasoconstrict and decrease choroidal blood flow, and the sensory input has been shown to both convey pain and thermal information centrally and act locally to vasodilate and increase choroidal blood flow. As the choroid lies behind the retina and cannot respond readily to retinal metabolic signals, its innervation is important for adjustments in flow required by either retinal activity, by fluctuations in the systemic blood pressure driving choroidal perfusion, and possibly by retinal temperature.

Influence of Spatial and Chromatic Noise on Luminance Discrimination.

Pseudoisochromatic figures are designed to base discrimination of a chromatic target from a background solely on the chromatic differences. This is accomplished by the introduction of luminance and spatial noise thereby eliminating these two dimensions as cues. The inverse rationale could also be applied to luminance discrimination, if spatial and chromatic noise are used to mask those cues.

Stimulation of Baroresponsive Parts of the Nucleus of the Solitary Tract Produces Nitric Oxide-mediated Choroidal Vasodilation in Rat Eye.

Preganglionic parasympathetic neurons of the ventromedial part of the superior salivatory nucleus (SSN) mediate vasodilation of orbital and choroidal blood vessels, via their projection to the nitrergic pterygopalatine ganglion (PPG) neurons that innervate these vessels. We recently showed that the baroresponsive part of the nucleus of the solitary tract (NTS) innervates choroidal control parasympathetic preganglionic neurons of SSN in rats. As this projection provides a means by which blood pressure (BP) signals may modulate choroidal blood flow (ChBF), we investigated if activation of baroresponsive NTS evokes ChBF increases in rat eye, using Laser Doppler Flowmetry (LDF) to measure ChBF transclerally.

Disinhibition of neurons of the nucleus of solitary tract that project to the superior salivatory nucleus causes choroidal vasodilation: Implications for mechanisms underlying choroidal baroregulation.

Preganglionic neurons in the superior salivatory nucleus (SSN) that mediate parasympathetic vasodilation of choroidal blood vessels receive a major excitatory input from the baroresponsive part of the nucleus of the solitary tract (NTS). This input appears likely to mediate choroidal vasodilation during systemic hypotension, which prevents decreases in choroidal blood flow (ChBF) due to reduced perfusion pressure. It is uncertain, however, how low blood pressure signals to NTS from the aortic depressor nerve (ADN), which fires at a low rate during systemic hypotension, could yield increased firing in the NTS output to SSN.

Color Discrimination Is Affected by Modulation of Luminance Noise in Pseudoisochromatic Stimuli.

Pseudoisochromatic stimuli have been widely used to evaluate color discrimination and to identify color vision deficits. Luminance noise is one of the stimulus parameters used to ensure that subject's response is due to their ability to discriminate target stimulus from the background based solely on the hue between the colors that compose such stimuli. We studied the influence of contrast modulation of the stimulus luminance noise on threshold and reaction time color discrimination.

The identification and neurochemical characterization of central neurons that target parasympathetic preganglionic neurons involved in the regulation of choroidal blood flow in the rat eye using pseudorabies virus, immunolabeling and conventional pathway tracing methods.

The choroidal blood vessels of the eye provide the main vascular support to the outer retina. These blood vessels are under parasympathetic vasodilatory control via input from the pterygopalatine ganglion (PPG), which in turn receives its preganglionic input from the superior salivatory nucleus (SSN) of the hindbrain. The present study characterized the central neurons projecting to the SSN neurons innervating choroidal PPG neurons, using pathway tracing and immunolabeling.

Low number of luminance levels in the luminance noise increases color discrimination thresholds estimated with pseudoisochromatic stimuli.

In pseudoisochromatic stimuli the presence of spatial and luminance noise forces the subject to discriminate the target from the background solely on the basis of chromaticity difference. Color-blind subjects may show difficulty to identify the target due to the elimination of borders and brightness clues caused by the luminance and spatial noise. Few studies have fully described the features of pseudoisochromatic stimuli.

Platelets, glycoprotein Ib-IX, and von Willebrand factor are required for FeCl(3)-induced occlusive thrombus formation in the inferior vena cava of mice.

Venous thromboembolism is a leading cause of death from cardiovascular disease. Despite the importance of the glycoprotein (GP) Ib-IX/von Willebrand factor (vWF) axis in arterial thrombosis, its requirement in venous, not venule thrombosis in response to endothelial injury (not stenosis or stasis) is uncharacterized. GPIbα-vWF participation in FeCl(3)-induced thrombus formation was evaluated in the inferior vena cava (IVC).

Age-related impairment in choroidal blood flow compensation for arterial blood pressure fluctuation in pigeons.

Purpose: Choroidal vessels compensate for changes in systemic blood pressure (BP) so that choroidal blood flow (ChBF) remains stable over a BP range of approximately 40 mm Hg above and below basal. Because of the presumed importance of ChBF regulation for maintenance of retinal health, we investigated if ChBF compensation for BP fluctuation in pigeons fails with age.

Methods: Transcleral laser Doppler flowmetry was used to measure ChBF during spontaneous BP fluctuation in anesthetized pigeons ranging in age from 0.

Immunohistochemical localization of AMPA-type glutamate receptor subunits in the nucleus of the Edinger-Westphal in embryonic chick.

The Edinger-Westphal nucleus (EW) in birds is responsible for the control of pupil constriction, accommodation, and choroidal blood flow. The activation of EW neurons is mediated by the neurotransmitter glutamate, in large part through AMPA-type glutamate receptors (GluRs), whose behavior varies according to the subunit composition. We investigated the developmental expression of the GluR subunits in EW of the chick (Gallus gallus) using immunohistochemistry on tissue from embryonic days 10 through 20 (E10-E20).

Projections from the hypothalamic paraventricular nucleus and the nucleus of the solitary tract to prechoroidal neurons in the superior salivatory nucleus: Pathways controlling rodent choroidal blood flow.

Using intrachoroidal injection of the transneuronal retrograde tracer pseudorabies virus (PRV) in rats, we previously localized preganglionic neurons in the superior salivatory nucleus (SSN) that regulate choroidal blood flow (ChBF) via projections to the pterygopalatine ganglion (PPG). In the present study, we used higher-order transneuronal retrograde labeling following intrachoroidal PRV injection to identify central neuronal cell groups involved in parasympathetic regulation of ChBF via input to the SSN. These prominently included the hypothalamic paraventricular nucleus (PVN) and the nucleus of the solitary tract (NTS), both of which are responsive to systemic BP and are involved in systemic sympathetic vasoconstriction.

Choroidal blood flow compensation in rats for arterial blood pressure decreases is neuronal nitric oxide-dependent but compensation for arterial blood pressure increases is not.

Choroidal blood flow (ChBF) compensates for changes in arterial blood pressure (ABP) and thereby remains relatively stable within a +/-40 mmHg range of basal ABP in rabbits, humans and pigeons. In the present study, we investigated if ChBF can compensate for increases and decreases in ABP in rats. ChBF was continuously monitored using laser Doppler flowmetry in anesthetized rats, and ABP measured via the femoral artery.

Essential and synergistic roles of RP1 and RP1L1 in rod photoreceptor axoneme and retinitis pigmentosa.

Retinitis pigmentosa 1 (RP1) is a common inherited retinopathy with variable onset and severity. The RP1 gene encodes a photoreceptor-specific, microtubule-associated ciliary protein containing the doublecortin (DCX) domain. Here we show that another photoreceptor-specific Rp1-like protein (Rp1L1) in mice is also localized to the axoneme of outer segments (OSs) and connecting cilia in rod photoreceptors, overlapping with Rp1.

Sustained upregulation of glial fibrillary acidic protein in Müller cells in pigeon retina following disruption of the parasympathetic control of choroidal blood flow.

Choroidal blood flow in pigeon eyes is light driven and controlled by a parasympathetic input from ciliary ganglion (CG) neurons that receive input from the medial subdivision of the ipsilateral nucleus of Edinger-Westphal (EWM). EWM lesions diminish basal ChBF and irreversibly prevent ipsilateral light-evoked increases in ChBF, presumably rendering the retina mildly ischemic. To characterize the location, severity, and time course of the retinal abnormality caused by an EWM lesion, we quantitatively analyzed the cellular and regional extent of Müller cell glial fibrillary acidic protein (GFAP) immunolabeling up to nearly a year after an EWM lesion.

Choroidal blood flow in pigeons compensates for decreases in arterial blood pressure.

While it had once been thought that choroidal blood flow (ChBF) does not compensate for changes in perfusion pressure, recent studies have shown that ChBF in rabbits and humans does compensate for changes in arterial blood pressure (ABP) and thereby remains relatively stable within a physiological range of ABPs. In this study, we sought to determine if ChBF in birds can compensate for decreases in ABP, either spontaneously occuring or caused by blood withdrawal. ChBF was continuously monitored using laser Doppler flowmetry in anesthetized pigeons, and at the same time ABP was measured via the brachial artery.

Effect of polyamine depletion on cone photoreceptors of the developing rabbit retina.

Purpose: To measure the concentrations of polyamines, determine their cellular and subcellular localization, and analyze effects of their depletion in developing rabbit retina.

Methods: Isolated retinas at different developmental stages were analyzed for polyamine content by high-performance liquid chromatography (HPLC). An antibody against polyamines was used to localize endogenous stores in both freshly harvested retinas and neonatal retinal explants.

Temporal relationship of choroidal blood flow and thickness changes during recovery from form deprivation myopia in chicks.

When form deprived, young chicks rapidly develop axial myopia, from which they recover if the treatment is ceased at a sufficiently early age. The increased axial growth of the eye is accompanied by choroidal thinning and decreased choroidal blood flow (ChBF). In contrast, during the early part of the recovery process, the choroid thickens, shifting the retina towards the new plane of focus.

Polyamine-dependent migration of retinal pigment epithelial cells.

Purpose: Migration of retinal pigment epithelial (RPE) cells can be triggered by disruption of the RPE monolayer or injury to the neural retina. Migrating cells may re-establish a confluent monolayer, or they may invade the neural retina and disrupt visual function. The purpose of this study was to examine the role of endogenous polyamines in mechanisms of RPE migration.