https://escholarship.org/content/qt2cz6r7bk/qt2cz6r7bk.pdf?t=poocnt

VEGF in Signaling and Disease: Beyond Discovery and Development.

Melatonin is uncommonly effective in reducing oxidative stress under a remarkably large number of circumstances. It achieves this action via a variety of means: direct detoxification of reactive oxygen and reactive nitrogen species and indirectly by stimulating antioxidant enzymes while suppressing the activity of pro-oxidant enzymes. In addition to these well-described actions, melatonin also reportedly chelates transition metals, which are involved in the Fenton/Haber-Weiss reactions; in doing so, melatonin reduces the formation of the devastatingly toxic hydroxyl radical resulting in the reduction of oxidative stress. Melatonin's ubiquitous but unequal intracellular distribution, including its high concentrations in mitochondria, likely aid in its capacity to resist oxidative stress and cellular apoptosis. There is credible evidence to suggest that melatonin should be classified as a mitochondria-targeted antioxidant. Melatonin's capacity to prevent oxidative damage and the associated physiological debilitation is well documented in numerous experimental ischemia/reperfusion (hypoxia/reoxygenation) studies especially in the brain (stroke) and in the heart (heart attack). Melatonin, via its antiradical mechanisms, also reduces the toxicity of noxious prescription drugs and of methamphetamine, a drug of abuse. Experimental findings also indicate that melatonin renders treatment-resistant cancers sensitive to various therapeutic agents and may be useful, due to its multiple antioxidant actions, in especially delaying and perhaps treating a variety of age-related diseases and dehumanizing conditions. Melatonin has been effectively used to combat oxidative stress, inflammation and cellular apoptosis and to restore tissue function in a number of human trials; its efficacy supports its more extensive use in a wider variety of human studies. The uncommonly high-safety profile of melatonin also bolsters this conclusion. It is the current feeling of the authors that, in view of the widely diverse beneficial functions that have been reported for melatonin, these may be merely epiphenomena of the more fundamental, yet-to-be identified basic action(s) of this ancient molecule.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/jpi.12360

Melatonin as an antioxidant: under promises but over delivers.

Surviving in a world with hidden rewards and dangers requires choosing the appropriate behaviours. Recent discoveries indicate that the habenula plays a prominent part in such behavioural choice through its effects on neuromodulator systems, in particular the dopamine and serotonin systems. By inhibiting dopamine-releasing neurons, habenula activation leads to the suppression of motor behaviour when an animal fails to obtain a reward or anticipates an aversive outcome. Moreover, the habenula is involved in behavioural responses to pain, stress, anxiety, sleep and reward, and its dysfunction is associated with depression, schizophrenia and drug-induced psychosis. As a highly conserved structure in the brain, the habenula provides a fundamental mechanism for both survival and decision-making.

/pdf/the-habenula-from-stress-evasion-to-value-based-decision-2yvxno84i2.pdf

The habenula: from stress evasion to value-based decision-making

Mechanisms of age-related macular degeneration

Understanding age-related macular degeneration (AMD): Relationships between the photoreceptor/retinal pigment epithelium/Bruch’s membrane/choriocapillaris complex

A rare type of ganglion cell in mammalian retina is directly photosensitive. These novel retinal photoreceptors express the photopigment melanopsin. They send axons directly to the suprachiasmatic nucleus (SCN), intergeniculate leaflet (IGL), and olivary pretectal nucleus (OPN), thereby contributing to photic synchronization of circadian rhythms and the pupillary light reflex. Here, we sought to characterize more fully the projections of these cells to the brain. By targeting tau-lacZ to the melanopsin gene locus in mice, ganglion cells that would normally express melanopsin were induced to express, instead, the marker enzyme beta-galactosidase. Their axons were visualized by X-gal histochemistry or anti-beta-galactosidase immunofluorescence. Established targets were confirmed, including the SCN, IGL, OPN, ventral division of the lateral geniculate nucleus (LGv), and preoptic area, but the overall projections were more widespread than previously recognized. Targets included the lateral nucleus, peri-supraoptic nucleus, and subparaventricular zone of the hypothalamus, medial amygdala, margin of the lateral habenula, posterior limitans nucleus, superior colliculus, and periaqueductal gray. There were also weak projections to the margins of the dorsal lateral geniculate nucleus. Co-staining with the cholera toxin B subunit to label all retinal afferents showed that melanopsin ganglion cells provide most of the retinal input to the SCN, IGL, and lateral habenula and much of that to the OPN, but that other ganglion cells do contribute at least some retinal input to these targets. Staining patterns after monocular enucleation revealed that the projections of these cells are overwhelmingly crossed except for the projection to the SCN, which is bilaterally symmetrical.

/pdf/central-projections-of-melanopsin-expressing-retinal-4shwej7y09.pdf

Central projections of melanopsin-expressing retinal ganglion cells in the mouse

Pigment epithelium-derived factor (PEDF) and vascular endothelial growth factor (VEGF) in aged human choroid and eyes with age-related macular degeneration

Orthostatic intolerance and chronic fatigue syndrome associated with Ehlers-Danlos syndrome.

Ehlers-Danlos syndrome☆☆☆

lmology a I dentification of children at risk for ambl essential first step toward the delivery of ti ment. The road to a superior vision scree egy comprises careful scrutiny of the availa ments and protocols as well as continued meth improvements and refinement. The study of R colleagues, whose work is reported in this is Journal, takes us on that road. In an attempt vision screening, the authors made two modi the manufacturer’s recommended methodolog justed the SureSight (Welch Allyn Medical Pro neateles Falls, NY) instrument’s failure criteri used the MTI PhotoScreener (PhotoScreener Springs, FL) instrument to achieve their des referral rate and higher positive predictive valu Children failing screening with the SureSi cutoff set to achieve 90% specificity and 63% underwent a second vision screening with the M Screener. Those with a crescent in any port photoscreening photograph failed screening. excellent method to identify children with hyp A different modification improves the ident those with supra-threshold astigmatic error. T find that a cutoff for the SureSight at 2.20 D children with 1.50 D of astigmatism by eye ex This higher cutoff improves the referral rate w taining the positive-predictive value and thus h ificity. Figure 1 of Rowatt et al has far more po the line with a slope of 1 through the origin t suggesting that the SureSight software tends t mate the magnitude of the astigmatic error. The algorithm for calculating astigmatism and likel fractive errors should be refined. The Rowatt report pointed out one differen their study and the VIP report: “the VIP stu evaluate children under age 3.” The two studie different means of patient recruitment, makin comparison of the results difficult. The particip VIP study were from a cohort failing an acuity-b Start vision screening program. In the Rowatt e

Patrick Tong

Papers

Central projections of melanopsin-expressing retinal ganglion cells in the mouse

Pigment epithelium-derived factor (PEDF) and vascular endothelial growth factor (VEGF) in aged human choroid and eyes with age-related macular degeneration

Orthostatic intolerance and chronic fatigue syndrome associated with Ehlers-Danlos syndrome.

Ehlers-Danlos syndrome☆☆☆

A road toward effective vision screening.