Macula

A disease process characterized by deterioration of the macula of the retina that results in a loss of shaip central vision. AMD is the leading cause of central vision loss in the developed countries today for those over the age of fifty years. 

Cyclooxygenase (COX) activity is responsible for the formation of prostaglandins from their arachidonic acid precursor. Two COX isoforms have been identified, COX-1 and COX-2. While COX-1 is constitutively expressed in most tissues, COX-2 is typically only found after induction by proinflammatory stimuli. However, a constitutively expressed and highly regulated COX-2 is found in the kidney, both in the renal medulla and in the renal cortex. Renal cortical COX-2 is located in the area ofthe juxtaglomerular apparatus, and prostaglandins formed by COX-2 regulate the expression and secretion of renin in response to a reduction in NaCl concentration at the macula densa. 

The macula densa is a dense aggregation of cells in the distal tubule of nephrons facing the glomerular tuft of capillaries. These cells sense the salt content of the distal tubular fluid and adjust glomerular perfusion and renin secretion accordingly. 

OTRs are mainly expressed in myoepithelial cells of the galactiferus channels and the myometrium. The OTRs in vascular endothelial cells, renal epithelial cells (macula densa, proximal tubule) and cardiomyocytes induce the production of NO (vasodilation), natriuresis and release of ANP, respectively. The endometrium, ovary, amnion, testis, epididymis, prostate and thymus also express the OTR supporting a paracrine role of this peptide. Osteoblasts, osteoclasts, pancreatic islets cells, adipocytes, and several types of cancer cells also express OTRs. More over, expression of the OTR... 

AMD is a deterioration of the central portion of the retina (the macula). The macula facilitates central vision and high-resolution visual acuity because it has the highest concentration of photoreceptors in the retina. The loss of central... 

Early macular changes are often called age-related macu-lopathy and are characterized by large drusen and pigmentary abnormalities in the macula.20 Age-related maculopathy accounts for 85% to 90% of all age-related macular changes. Ten to fifteen percent of these patients will develop advanced atrophy and/or develop abnormal blood vessels in and under the retina called choroidal neovascular membranes. Patients are then classified as having AMD.23... 

Dilated fundus examination shows drusen and pigmentary abnormalities in the macula... 

Macula An oval, yellow-pigmented area on the central retina containing color-sensitive rods and the central point of sharpest vision. 

Schalch, W. (2001). Possible contribution of lutein and zeaxanthin, carotenoids of the macula lutea, to reducing the risk of age-related macular degeneration A review. HKJ Ophthalmology 4 31—42. 

Levels of carotenoids are much lower in the skin relative to the macula of the human eye, but higher light excitation intensities and longer acquisition times can be used in Raman detection approaches to compensate for this drawback. Since the bulk of the skin carotenoids are in the superficial layers of the dermis, and since the concentrations are relatively low, the thin-film Raman equation given above, Equation 6.1, should still be a good approximation. 

Bhosale, P., A. J. Larson, K. Southwick, C. D. Thulin, and P. S. Bernstein. 2004. Identification and characterization of a Jt-isoform of glutathione S-transferase (GSTP1) as a zeaxanthin-binding protein in the macula of the human eye. J. Biol. Chem. 279 4944749454. 

The horizontal distribution (Figure 13.4, top) of the macular xanthophylls across the retina has been studied in detail by measuring concentrations in postmortem eyes via HPLC (Bone et al. 1997). The macular xanthophylls are detectable across the entire retina but have their highest concentration in the center of the macula. The local zeaxanthin to lutein ratio depends on the distance from the fovea and decreases from about 2 1 at its center to a low of near 1 2 in the peripheral retina. The variation in the zeaxanthin/lutein ratio across the retina suggests that the chemical and biochemical influences operating on the xanthophylls in the peripheral retina are different from those in the central macula. This is an area about which not much is known and would constitute an interesting field of research. 

As already mentioned, macular zeaxanthin comprises two stereoisomers, the normal dietary (3/(,37()-/caxanthin and (3f ,3 S)-zeaxanthin(=(meyo)-zeaxanthin), of which the latter is not normally a dietary component (Bone et al. 1993) and is not found in any other compartment of the body except in the retina. The concentration of (tneso)-zeaxanthin in the retina decreases from a maximum within the central fovea to a minimum in the peripheral retina, similar to the situation with (3/ ,37 )-zeaxanthin. This distribution inversely reflects the relative concentration of lutein in the retina and gave rise to a hypothesis (Bone et al. 1997) that (meso)-zeaxanthin is formed in the retina from lutein. This was confirmed by an experiment in which xanthophyll-depleted monkeys had been supplemented with chemically pure lutein or (3/ ,37 )-zeaxanthin (Johnson et al. 2005). (Meyo)-Zeaxanthin was exclusively detected in the retina of lutein-fed monkeys but not in retinas of zeaxanthin-fed animals, demonstrating that it is a retina-specific metabolite of lutein only. The mechanism of its formation has not been established but may involve oxidation-reduction reactions that are mediated photochemically, enzymatically, or both. Thus, (meso)-zeaxanthin is a metabolite unique to the primate macula. 

The observation that lutein and zeaxanthin occur in the highest concentration in the macula soon raised expectations that the macular xanthophylls may be essential in maintaining structure and function of the retina by contributing not only to risk reduction of macular diseases but also to improving visual performance of the healthy eye, which was the original hypothesis to explain the presence of the macular yellow pigment as mentioned previously. 

The evidence available to date indicates that lutein and zeaxanthin could contribute to achieving the last two objectives, namely, the reduction of actinic insults caused by blue light and quenching reactive oxygen species. This follows from the dual presence of xanthophylls in the macula their prereceptoral location and their presence within the outer segments themselves, as discussed in Section 13.5. 

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