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| September 2003 | Inside IOVS | Volume 44/9 |
Intrinsic Choroidal Neurons
Intrinsic choroidal neurons (ICN) represent a peculiar cell population residing within the choroid in both birds and higher primates. They may control functions of the choroid, e.g. choroidal blood flow or changes in choroidal thickness. Schrödl et al. (p. 3705) adopted a technique which allowed for the electrophysiological characterization of ICN in human donor tissue and subsequent filling of these neurons with a dye-like substance. By doing so, targets of these neurons could be identified: ICN via intrinsic contacts, blood vessels and stromal non-vascular smooth muscle cells. The technique renders further pharmacological experiments feasible, providing better insight into neuronal regulation of ocular homeostasis.
Construction of a Human Retina Custom cDNA Microarray
Microarrays are a recent technology that enables high throughput gene expression profiling. Chowers et al. (p. 3732) describe the construction of a human retinal custom cDNA microarray that includes more than 10,000 sequences from known and novel genes. The authors have employed this microarray to identify 186 genes, about half of them novel, that demonstrate a previously uncharacterized retina-enriched expression pattern. Interestingly, the analyses showed that most of these genes are also expressed in multiple additional tissues. These genes are likely to include some that are important in maintaining normal retinal function, as well as potential candidate genes for retinal disease.
Atherosclerosis and Age-Related Maculopathy
The relation between atherosclerosis and age-related maculopathy is still much debated. In the population-based Rotterdam Study, non-invasive techniques were employed to detect systemic atherosclerotic changes, and the incidence of age-related maculopathy was determined after a mean follow-up of 5.2 years. Van Leeuwen et al. (p. 3771) showed that sub-clinical atherosclerosis, in particular of the carotid artery, is associated with an increased risk of age-related maculopathy. This finding suggests that a reduction in the high prevalence of atherosclerosis and its risk factors may add to the prevention of this blinding disease.
Accurate Intraocular Pressure Measurements after Corneal Refractive Surgery
Corneal refractive surgery alters the indentation properties of the cornea and leads to inaccurately low central applanation tonometry measurements. Kaufmann et al. (p. 3790) compared Goldmann applanation tonometry (GAT) with a new tonometry principle that is not based on the assumption of a standard corneal structure. In patients following LASIK for myopia they found a significant decrease in intraocular pressure measurements using GAT whereas the new dynamic contour tonometry (DCT) provided stable pressure readings. The authors conclude that DCT in these patients represents a valuable alternative to adjustments of applanation tonometry readings such as nomograms or conversion factors.
Conjunctival b-Defensin Expression and Dry Eye
Dry eye is characterized by damage to the corneal and conjunctival epithelia. However, this does not appear to be associated with an increase in the occurrence of infections, suggesting alternate mechanisms of ocular surface defense. Narayanan et al. (p. 3795) found that human conjunctival epithelium express antimicrobial human b-defensins (hBD). Notably, hBD-2 was expressed only in dry eye subjects and it was upregulated in cultured conjunctival cells by proinflammatory cytokines and heat-killed Pseudomonas aeruginosa. The authors speculate that hBD-2 upregulation observed in dry eye subjects provides additional antimicrobial protection and may be a consequence of enhanced proinflammatory cytokine activity.
FGF-2 and Corneal Storage
Unexpected loss of viability and number of endothelial cells after organ-culture donor corneal preservation is often due to a reduced quality of fetal calf serum (FCS) preparations routinely added to standard organ-culture media. An additional risk of prior disease (e.g., BSE) transmission via FCS emphasizes the need for the development of a serum-free organ-culture medium. Rieck et al. (p. 3826) demonstrate that FGF-2 added to serum-free standard media efficiently reduces human corneal endothelial damage occurring during organ-culture storage. This effect is truly protective since no proliferative activity, but a decreased rate of apoptosis could be determined. FGF-2 could thus represent an important component of a future defined serum-free corneal organ-culture medium.
Vascular Endothelial Growth Factor (VEGF-A) and Lens Development
In mammals, the fetal lens is surrounded by capillaries that later regress. Shui et al. (p. 3911) show that VEGF-A protein is expressed in the lens adjacent to where these capillaries are forming, suggesting that VEGF-A from the lens regulates the formation of the fetal vasculature. They also find that, later in development and in adults, VEGF-A levels in the lens are regulated by hypoxia. Surprisingly, one of the receptors for VEGF is present in the lens and this receptor is normally activated in vivo. This raises the possibility that other aspects of lens development and growth are regulated by VEGF signaling.
Newly Identified Photoreceptor Cell Protein
5A11/Basigin-2, a newly identified member of the immunoglobulin gene superfamily, is selectively expressed by photoreceptors, with greatest expression during development of the retina. Loss of the gene for this protein causes blindness and eventual retinal degeneration. A comparison of 5A11/Basigin-2 protein sequences from mouse, rat, human, chicken, and zebrafish indicates that a region of the extracellular domain is highly conserved through evolution. These data, reported in Ochrietor et al. (p. 4086), suggest that 5A11/Basigin-2 has a highly specific role in photoreceptor development. Future studies aimed at discerning the function of this protein will further the understanding of photoreceptor development and lead to therapies for outer retinal dystrophies.
Vision Care Services in South African Children
A survey of urban and semi-rural school-age African children conducted by Naidoo et al. (p. 3764) provides credible evidence of the inadequacies of primary eye care services in South Africa. An unexpectedly high prevalence of corneal and anterior segment abnormalities was found in a population-based, random sample of low-middle socioeconomic children. Although reduced vision was found to be relatively uncommon, 80% of those requiring refractive correction were without the necessary spectacles. Given the paucity of reliable prevalence data, these findings will serve as a basis upon which service delivery challenges in South Africa and neighboring countries can be addressed.
Hyperopia and Age-Related Maculopathy
The nature of the association between hyperopia and age-related maculopathy (ARM) is still unclear, and may provide insight into the pathogenesis of this disease. Ikram et al. (p. 3778) showed that both in a cross-sectional as well as in a follow-up analysis the risk of developing ARM was increased by 5-9% per diopter of increasing hyperopia. In view of these findings, special attention should be given to older persons with hyperopia (e.g. over 70 years with hyperopia > 3.0 diopter) in order to offer them the potential benefit of micronutrient supplementation for prevention of ARM.
Superior Oblique Is Not Unique: Inferior Oblique Has Its Pulley, Too
We’ve always known that the superior oblique muscle has a rigid pulley, the trochlea. The inferior oblique (IO) didn’t seem to have a pulley. Using magnetic resonance imaging and histology in humans and monkeys, Demer et al. (p. 3856) now have demonstrated a soft pulley encircling the IO muscle. The IO pulley is actively moved by the orbital layers of both the IO and inferior rectus muscles. Movements of the IO pulley coordinate with active control of rectus muscle pulleys to facilitate neural control of binocular alignment. Age-related degeneration of the IO pulley may cause strabismus in older people.
How Much Ciliary Blood Flow Is Needed To Sustain Aqueous Production?
Although aqueous formation is known to require the expenditure of metabolic energy, the relationship between aqueous production and the delivery of metabolic fuel by ciliary blood flow is unknown. Reitsamer and Kiel (p. 3967) used mechanical manipulations of blood pressure to vary ciliary blood flow in rabbits and found that aqueous production is blood flow-independent until ciliary blood flow falls below 74% of its control level; below that level, aqueous production is blood flow-dependent. This finding supports an old hypothesis that some glaucoma drugs inhibit aqueous production by vasoconstricting the ciliary circulation and depriving the ciliary epithelia of the fuel needed to sustain aqueous production.
Retinal Neuroprotective Effect of Cardiotropin-1
Cardiotropin-1 (CT-1) is a member of the interleukin-6 (IL-6) family of cytokines that includes LIF (leukemia inhibitory factor) and CNTF (ciliary neurotrophic factor). Using a transgenic rat model of photoreceptor degeneration, Song et al. (p. 4069) describe a potent neuroprotective effect of CT-1 on photoreceptors and show that repeated dosing extends the effect. They also demonstrate that CT-1 activates the STAT3 signaling pathway in Müller cells. This study points out the importance of sustained delivery of neurotrophic factors for long-term effects and highlights the crucial role of a gp130-dependent mechanism in Müller cells in photoreceptor protection.
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