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Footnotes:

 

 

95. HALASA AH. Ocular Manifestations of nutritional diseases. In: MANSOLF FA, ed. The Eye and Systemic Disease, ch. 7. St. Louis: C. V. Mosby, 1975: pp. 141, 143, 144, and 149.

 

 

96. SMITH CG, GALLIE BL, MORIN JD. Normal and Abnormal Development of the Eye. In: CRAWFORD JS, DONALD MJ. The Eye in Childhood. New York: Grune & Stratton, 1983: P. 11 (top right).

 

 

97. KRETZER FL, MCPHERSON AR, HITTNER HM. An interpretation of retinopathy of prematurity in terms of spindle cells: relationship to vitamin A prophylaxis and Cryotherapy. Graefe's Arch Clin Exp Ophthalmol 1986: 224: 205-14.

 

 

98. RICCI B, CALOGERO G. Oxygen-induced retinopathy in newborn rats: Effects of prolonged normobaric and hyperbaric oxygen supplementation. Pediatrics 1988: 82: 193-8 (see page 196 middle left and top right).

 

 

99. EDELMAN GM. Topobiology - An Introduction to Molecular Embryology. New York: Basic Books. 1988: pp. 61, 201-3.

 

 

100. KURABARA T, GORN RA. Retinal damage by visible light. Arch Ophthalmol 1968: 79: 69-70.

 

 

101. KREZER FL, HITTNER HM, JOHNSON AT, MEHTA RS, GODIO LB. Vitamin E and retrolental fibroplasia: Ultrastructural support of clinical efficacy. Ann New York Acad Sci 1982: 393: pages 145-66 (see pages 149 and 152).

 

 

102. KRETZER FL, HITTNER HM. JOHNSON AT, MEHTA RS, GODIO LB. Vitamin E and retrolental Fibroplasia: Ultrastructural support of clinical efficacy. Ann New York Acad Sci 1982: 393: pages 145-66. Ref. 101, see page 156 bottom.

 


 


 

  

 

  

  Preemies get more retinal irradiance

 

than safety guidelines allow for adults 

 
 

DavidNurs03.jpg (22659 bytes)

Baby-blinding retinopathy of prematurity and intensive care nursery lighting
by H. Peter Aleff

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3.) Self-repair: The fact that not all preemies lose their eyesight but many recover from the early stages of ROP shows that they have a remarkable developmental plasticity. On the other hand, the fact that many suffer permanent eye damage shows that this ability to cope with disturbances to their normal development can be overwhelmed.

Adults and children would all go blind if the light damage to our retinae accumulated indefinitely. Mature light receptors dissipate most of the absorbed energy by transforming the rhodopsin in the rod tip into a Vitamin A ester. This Vitamin A ester then goes through a regeneration period in darkness during which it converts back into rhodopsin (95).

Light energy which we do not dissipate in this way destroys the retinal structures that absorb it. Like the skin -- the only other organ exposed to light - the retina renews its molecular components on a regular basis. The light receptors shed their outer segments daily, and the scavenging macrophages in the underlying retinal tissue reabsorb them. This normal turnover of the outer segments takes about 10 to 15 days (93).

Preemies are often exposed to bright nursery lights around-the-clock. They do not yet have mature light receptors and could not dissipate the arriving photons even if they were allowed a rest period in the dark. Furthermore, their developing retinal blood vessels are easily disturbed.

If there was an intensity threshold below which light does not damage preemie eyes, even during prolonged exposure, this threshold would have to be much lower than for adults. There may not be a threshold below which light is safe for eyes that are not ready to receive it.

The light receptors will be able to do their light-receiving job only at about term. Just like the cells which will become retinal blood vessels, the light receptors develop relatively late in gestation and do not start their migration before the 6th month (96). They also start out from the optical disc and reach the front of the eye by the 32nd week.

Only then do they begin to grow mitochondria, the minute thread like bodies without which no cell can have a metabolism. The full "fleshing out" of this structure into permanent light receptors continues post-term (97). Until all the light receptors are in full working order, much of the energy which irradiates the preemie's and even term-baby's retina can, therefore, not be conducted away safely by the decay of rhodopsin into Vitamin A ester, as in older people.

The mechanism by which light damages mature eyes is known from countless animal experiments in which monkeys and rats and other animals, usually several weeks old or older, have been systematically exposed to light of different wavelengths and intensities for different lengths of time.

The retinal blood vessels of some animals (for instance: the kitten, the puppy, the rat) reach maturity only 2 to 3 wk after birth (98). Nature protects these animals by keeping their thick eyelids fused shut until their eyes are ready for light.

But the eyes of most animals in the light-exposure tests were more mature than those of preemies. The light exposures in these experiments destroyed the photo-receptors of the test animals but did not usually affect the development of the already mostly formed blood vessels in their retinae.

Cells that have settled down from their fetal migration and are anchored as part of a blood-vessel wall are quite resistant to light damage, and the relatively stable structure of which they form a part can self-repair. But the cells in the retina of our preemie are still traveling and are easily led astray if something changes their road maps.

Light does just that. It hits the surfaces of the still migrating and developing cells which will later form the light receptors and the retinal blood vessels. These surfaces are covered with lipid molecules which contain the code for the migration path of the cells. They also feature an array of different receptors (not to be confused with the much larger light receptors of which some of these cells will become a part). These cell-surface receptors sense their surroundings and thus receive the signals as to the direction in which the cell should migrate.

Like ships that follow a chart but adjust their course according to information they receive about winds and currents, the cells follow their encoded road map but change their path of migration according to the messages they receive. They possess a number of mechanisms to react to these messages from their environment; these mechanisms govern cell shape, cell motion, and cell division. The migration road map encoded on the cell surface is easily changed by anything that disturbs the delicate balance of surface receptors and reaction mechanisms.

Dr. Gerald M. Edelman studied the place-dependent interactions at the surfaces of living cells that regulate the processes of embryological development. He describes how this code evolves in response to the cell's surroundings:

"Neuronal patterns are not assured by preassigned molecular addressing on each cell to construct a 'jigsaw puzzle' pattern by which networks are hardwired. Instead, a relatively small number of cell adhesion molecules and substrate adhesion molecules on the surface of cells switch on and off in sequences defined by their local environment. This dynamic switching changes the patterns of cell motion, of process attachment, and, ultimately, of the connections formed. Perturbations of this switching lead to changes in Cell Adhesion Molecule expression and distribution (99).

Under the random impact of photons from fluorescent irradiation, the cell receives garbled messages that make it move elsewhere. By the time it arrives at the new destination and there transform itself into a piece of vessel wall, it forms with the other misdirected cells a tangle of vessels that proliferate and grow tortuously into the vitreous.

Electron microscopic studies
of damage from light and from ROP

The chaos resulting from the garbled messages can be observed under the electron microscope. The high magnification shows clearly that light damage and ROP both cause the same changes at the cellular level.

Electron microscope pictures of light-damaged retina segments from albino rats (100) show that after exposure to light the cell membranes of the photoreceptors and of the pigment epithelium cells form massive microvilli, little hairlike tendrils, which grip each other like the hooks and loops on a patch of Velcro. This causes the cell membranes to stick together permanently.

Electron microscopes have also been used to observe retina samples from deceased preemies who had developed the earliest stages of ROP (101). These pictures show the same cross-linking of tendrils and of many surface microvilli on the spindle cells of all of 4 infants with ROP, as opposed to very few microvilli on the spindle cells of the infants without the disease.

These findings led the authors to the working hypothesis, which has become accepted medical opinion, "that the linkage of spindle cells by gap junctions inhibits migration of new vessels, primes spindle cell proliferation anterior to the shunt, and triggers neovascularization posterior to the shunt" (102). The shunt, in this context is the area nowhere the vessels stop advancing and grow towards each other to form loops.

The gap junctions show up in the pictures of ROP retinae as areas of contact between adjacent cells permanent adhesions between the microvilli of the spindle cell membranes, just like the permanent adhesions between the microvilli of the cell membranes in the pictures of light-damaged retinae.

The spindle cells are the building blocks for the developing, retinal blood vessels. At the end of their migration these cells become the walls of the capillaries. Anything that interferes with the free migration of these cells must therefore interfere with the formation of the capillaries which these same cells will become.  Just as in ROP.

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