The role of perinatal stress in simplex retinitis pigmentosa: evidence from surveys in Australia and the United States.

Background: In experimental models of several forms of human retinitis pigmentosa (RP) the dystrophy begins in the neonatal period, during a "critical period" in which photoreceptors are sensitive to hypoxia. We performed a study to test whether perinatal stress is associated with human RP, particularly in simplex (nonfamilial) cases.

Methods: Two surveys were carried out in 1999.

Effects of oxygen and bFGF on the vulnerability of photoreceptors to light damage.

Purpose: To test whether tissue oxygen levels affect the vulnerability of photoreceptors to damage by bright continuous light (BCL).

Methods: Albino rats were raised in standard conditions of cyclic light (12-hour light, 12-hour darkness) with the light level at 5 to 10 lux or 40 to 65 lux. They were then exposed to BCL (1000-1400 lux), either continuously for 48 hours or for the day or night components of the 48-hour period.

The human hyaloid system: cell death and vascular regression.

The present study had investigated the roles of apoptosis and necrosis in the regression of the human fetal hyaloid vasculature. Normal human fetal hyaloid specimens (n = 67) ranging from 10 to 20 weeks' gestation were studied. Specimens were either immunolabeled with anti-von Willebrand factor and major histocompatibility complex class I antibodies or investigated using the terminal-deoxyribonucleotidyl transferase-mediated dUTP-biotin DNA nick-end labeling technique.

Mechanisms of photoreceptor death and survival in mammalian retina.

The mammalian retina, like the rest of the central nervous system, is highly stable and can maintain its structure and function for the full life of the individual, in humans for many decades. Photoreceptor dystrophies are instances of retinal instability. Many are precipitated by genetic mutations and scores of photoreceptor-lethal mutations have now been identified at the codon level.

Limiting the proliferation and reactivity of retinal Müller cells during experimental retinal detachment: the value of oxygen supplementation.

Purpose: To assess the role of hypoxia in inducing the proliferation, hypertrophy, and dysfunction of Muller cells in detached retina and the effectiveness of supplemental oxygen in limiting these reactions.

Methods: Retinal detachments were produced in the right eye of each of 13 cats; the cats survived surgery for 3 days, during which six were kept in normoxia (room air, 21%) and seven in hyperoxia (70% oxygen). Retinas were labeled for proliferation with an antibody (MIB-1) to a cell cycle protein (Ki-67), for evidence of hypertrophy employing antibodies to the intermediate filament protein glial fibrillary acidic protein (GFAP) and to beta-tubulin and for disturbance of glutamate neurochemistry employing antibodies to glutamate to a glutamate receptor (GluR-2) and to glutamine synthetase.

Limiting photoreceptor death and deconstruction during experimental retinal detachment: the value of oxygen supplementation.

Purpose: To assess the role of hypoxia in causing the death and deconstruction of photoreceptors in detached retinas and the effectiveness of supplemental oxygen in limiting such damage.

Methods: Retinal detachment was induced surgically in the right eye of each of 10 cats. The cats were allowed to survive surgery for 3 days.

Photoreceptor dystrophy in the RCS rat: roles of oxygen, debris, and bFGF.

Purpose: To examine the roles of oxygen, basic fibroblast growth factor (bFGF), and photoreceptor debris in the photoreceptor dystrophy of the Royal College of Surgeons (RCS) rat.

Methods: Pups were exposed during the critical period of their development (postnatal day [P] 16-24) and for some days thereafter to hypoxia and hyperoxia. The effects of these exposures on photoreceptor death, debris accumulation in the subretinal space, and the expression of bFGF protein and mRNA by surviving cells were studied.

Tissue oxygen during a critical developmental period controls the death and survival of photoreceptors.

Purpose: To study the death of photoreceptors in normally developing and dystrophic retina and to test the role of hypoxia in causing that death.

Methods: Death of photoreceptors was detected in the albino, hooded, and Royal College of Surgeons (RCS) strains of rat, and in the rabbit and cat, using the TUNEL technique. Retinas of selected ages from animals raised normally and those from rat pups raised for periods in hyperoxia (75% oxygen) or hypoxia (10% oxygen) were studied.

Fate of DNA from retinal cells dying during development: uptake by microglia and macroglia (Müller cells).

The tunel technique of labelling fragmenting dna was used to examine cell death in the developing retina of the rabbit, rat and cat. TUNEL-labelled structures included the still-intact nuclei of retinal cells and smaller, strongly labelled bodies interpreted as fragments of disintegrating nuclei (apoptotic or pyknotic bodies). With confocal microscopy, the cytoplasm around labelled nuclei was observed to be labelled, suggesting that DNA fragments spread into the cytoplasm of the dying cell.

Ontogeny of catecholaminergic and cholinergic cell distributions in the cat's retina.

The development of catecholaminergic and cholinergic neurones in the cat's retina has been examined with antibodies against their respective rate-limiting enzymes, tyrosine hydroxylase (TH) and choline acetyl transferase (ChAT). ChAT-immunoreactive (IR) cells were first detected at E (embryonic day) 56 with somata in the ganglion cell layer (GCL) or in the inner cytoblast layer (CBL). At P (postnatal day) 1, two faint bands of ChAT-IR fibres were evident in an inner and outer strata of the inner plexiform layer (IPL) and by P26, the bands were similar to those in the adult.

Extracellular space in the developing retina assessed by electron microscopy: laminar and topographic distribution.

The extent of extracellular space (ECS) in the developing retina of the cat has been measured by electron microscopy in material fixed using techniques developed by others to preserve ECS. ECS is generally greater in foetal than in adult material. It is particularly marked in the plexiform layers of retina at the time of synaptogenesis and in the axon layer at the time of axon growth.

Time course of stratification of the dendritic fields of ganglion cells in the retina of the cat.

The inner plexiform layer (IPL) of the retina has been shown by previous workers to comprise a number of sublayers (sublaminae or strata), each containing a distinct component of its circuitry. Using horseradish peroxidase applied to cultured whole retinas, we have observed the segregation of the dendrites of ganglion cells of the cat retina into two sublayers of the IPL. These sublayers appear to correspond to the a and b sublaminae described in studies of the adult IPL.

Catecholaminergic and cholinergic neurons in the developing retina of the rat.

We have examined the development of catecholaminergic and cholinergic neurons in the retina of the rat by using antibodies against the enzymes tyrosine hydroxylase (TH) and choline acetyl transferase (ChAT), respectively. TH-immunoreactivity was first detected at P (postnatal day) 3 in somata located in the inner part of the cytoblast layer (CBL) and in fine dendrites extending toward the middle of the inner plexiform layer (IPL). These cells were similar in shape and soma size to the class 2 TH-immunoreactive (TH-IR) cells of the adult rat.

Stages in the structural differentiation of retinal ganglion cells.

Using a cultured wholemount technique we have studied the morphological differentiation of ganglion cells in the retina of the rat and cat, during normal development. In both species the differentiation of ganglion cells begins in embryonic life, before embryonic day (E) 17 in the rat and E36 in the cat. It is useful to describe the morphological differentiation of ganglion cells as occurring in three stages.

Synaptogenesis in the retina of the cat.

We have studied the development of synapses in the retina of the cat from E(embryonic day)21 to adulthood. The inner plexiform layer (IPL) could be distinguished by E36, but at this age no synapses had formed, although compact processes had formed in the IPL and membrane specialisations had developed in adjacent processes. Conventional synapses form in the IPL from E45 and become increasingly numerous and differentiated over subsequent weeks.