Retinitis Pigmentosa, Eye Infections, Retinitis & Lutein & Zeaxanthin. Zealut-Dena

BENEFITS OF TAKING ZEALUT-DENA (LUTEIN AND ZEAXANTHIN) FOR PATIENTS WITH RETINITIS PIGMENTOSA

Retinitis pigmentosa is a heterogenous group of hereditary conditions that lead to gradual retinal degeneration that results from progressive loss of rod and cone photoreceptor cells and results in the loss of night vision (provided by rod photoreceptor neurons) in adolescents, followed by the loss of side vision in young adults (which causes so-called "tunnel vision"), and finally by the loss of central vision (high-acuity daylight vision, provided by cone photoreceptors) [1, 2]. Despite similar disease progression, the etiology of retinitis pigmentosa is different in different patients, with causative mutations identified in >45 genes [1]. However, in many patients, the exact causes of the disease remain unknown.

 

Oxidative stress is well known to contribute to the onset and progression of a number of eye diseases. In retinitis pigmentosa, oxidative stress primarily contributes to the loss of central vision, likely because cones become vulnerable after the death of rods, which constitute approximately 90% of all photoreceptor neurons and neutralize most reactive oxygen species; in addition, cones have higher content of mitochondria, which produce most reactive oxygen species during respiration [2].

 

Although multiple carotenoid species are present in blood plasma, only lutein and zeaxanthin are able to cross the hemato-ophthalmic barrier and accumulate in the eye tissues, including the retina, where their concentration is four orders of magnitude higher than in the blood [3, 4]. These carotenoids are thought to protect the retina in a dual way: by filtering out the most damaging short-wavelength irradiation (blue light and UV) and by scavenging reactive oxygen species [5, 6].

 

Within the retina, lutein and zeaxanthin are concentrated in the macula and form so-called macular pigment. As much as 25% of total retinal content of these carotenoids is found in the outer segments of the rod photoreceptor neurons [7] (which are lost first in the course of retinitis pigmentosa progression [1, 2]), where the light receptor rhodopsin and enzymes of its downstream signaling cascade are located. Since rods are much more sensitive to light and therefore to photodamage than cone photoreceptors, accumulation of carotenoids in rod outer segments suggests a direct function of lutein and zeaxanthin in rod protection from photodamage.

 

The content of macular pigment depends on the dietary intake of lutein and zeaxanthin and follows changes in the uptake of these carotenoids with a delay of two to three weeks [8]. In retinitis pigmentosa patients, macular pigment was found to increase with increasing serum concentration of lutein but not zeaxanthin [9]. Thus, supplementation with at least lutein could be expected to be beneficial for retinitis pigmentosa patients (it should be noted that lutein is the main component of Zealut-Dena).

 

Consistent with these data, taking lutein (20 mg/day) for six months significantly increased the content of macular pigment in patients with retinitis pigmentosa and Usher syndrome (a combination of retinitis pigmentosa and a sensorineural hearing loss) [10], choroideremia (a congenital X-linked retinal degeneration) [11], CRB1–associated retinal degeneration [12, 13], and ABCA4-associated retinal degeneration [13], although it was not accompanied by a statistically significant improvement in central vision during the study periods, suggesting that either lutein has no benefit for patients with these diseases, or its effect takes longer than six months to develop.

 

A number of studies have assessed the effects of supplementation with lutein the progressive decline in visual function in retinitis pigmentosa patients. A small-scale study on 13 retinitis pigmentosa patients [14] reported beneficial effects of taking a higher dose of lutein (40 mg/day for nine weeks, followed by 20 mg/day for 15 weeks). The authors found improvements in visual acuity and mean visual-field area, which were detectable as early as two to four weeks after the beginning of treatment and plateaued at 6–14 weeks. Curiously, blue-eyed participants benefited more from lutein intake than dark-eyed participants.

 

Berson and coworkers [15] investigated the effects of lutein (12 mg daily, i.e. similar to the content in one capsule of Zealut-Dena) on the decline in visual function in retinitis pigmentosa patients who received vitamin A. Lutein was found to slow the loss of the mid-peripheral visual field; the patients with the highest macular pigment content showed the slowest decline in field sensitivity, supporting the causal link between lutein and visual function. The strong points of this study were that it enrolled a considerable number of patients (225) and the observation period was as long as four years, with no signs of lutein toxicity noted over this period.

 

A study conducted at Johns Hopkins University using a cohort consisting of 44 retinitis pigmentosa patients and 11 patients with related retinal degenerations [16] reported no significant effects of lutein (10 mg/day for 12 weeks and 30 mg/day for the following 12 weeks) but found a trend towards improvement in visual acuity and contrast sensitivity, although none of these effects reached statistical significance. Potentially important could be the observation that 11 out of 13 subjects who decided to withdraw from the study were receiving placebo; this might indicate that lutein supplementation had positive effects that were not quantified in the study but were perceived by the participants.

 

A later study at the same university [17] assessed the effect of lutein on visual acuity and contrast sensitivity. The choice of the subjects (36) was restricted to retinitis pigmentosa; the same lutein supplementation scheme was used. In this study, lutein significantly improved central visual field with an estimated six-week delay. As in the first study, there was also a tendency towards improvement in visual acuity, although it did not reach statistical significance. Safety of lutein supplementation was also noted.

 

A decline in visual acuity in retinitis pigmentosa patients is due not only to the loss of photoreceptor cells, but also to retinal thickening, which is thought to be due to edema [18]. Lutein alone administered for 48 weeks was reported to have no significant effect on retinal thickness in retinitis pigmentosa patients regardless of the presence or absence of cystoid macular edema [19]. However, Hu and coworkers [20] found that supplementation with lutein (6 mg/day) and zeaxanthin (0.5 mg/day) for three months significantly improved visual acuity, contrast sensitivity, and macular edema in patients with nonproliferative diabetic retinopathy. Taking into account heterogeneity of retinitis pigmentosa, it seems reasonable to assume that supplementation with these carotenoids might have a similar effect in some cases of retinitis pigmentosa as well.

 

Some discrepancies between the results of different studies is perhaps not surprising, because retinitis pigmentosa is a very heterogenous group of diseases caused by mutations in several dozens of different genes, and in many cases the underlying genetic cause of retinal degeneration remains unknown. Overall, although the details of the role lutein and zeaxanthin in slowing down the decline in visual function in patients with this disease remain to be investigated, the data available to date indicate that high doses of lutein and/or long treatment periods may be most beneficial for retinitis pigmentosa patients.

 

References

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  10. Aleman, T.S. et al. Macular pigment and lutein supplementation in retinitis pigmentosa and Usher syndrome. Invest Ophthalmol Vis Sci 42, 1873-1881 (2001).
  11. Duncan, J.L. et al. Macular pigment and lutein supplementation in choroideremia. Exp Eye Res 74, 371-381 (2002).
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