Retinitis Pigmentosa

WEB EXCLUSIVE

Updated Data Regarding Pathogenesis and Implications for Natural Therapeutics
Paul S. Anderson, ND

Retinitis pigmentosa (RP) is a heterogeneous group of inherited retinal disorders that are characterized by progressive degeneration of the photoreceptors and the underlying retinal pigment epithelium.1 Given its prevalence of 1 case among 3000 to 5000 individuals, RP is the most common group of inherited retinal diseases.2,3 Signs and symptoms often include slowly progressive bilateral loss of night vision. A ring scotoma is often present on perimetry, which tends to widen the decreasing central vision. Dark “bone spicule” pigment changes are frequently seen in the retina. Diagnostic investigations include perimetry, dark adaptation testing, and electroretinographic studies.

Natural therapeutic interventions have been limited, but popular inclusion of retinol in complementary and alternative medicine (CAM) therapies followed original work by Berson et al4 in 1993. Natural therapeutics, including retinol, lutein, and docosahexaenoic acid have shown promise in slowing the progression of RP.5-9 In the past, conflicting and unclear data have been reported that seemed to point to a negative sensitivity of patients with RP to vitamin E supplementation4 and some derangement of amino metabolism in patients with RP,10 which led to no new biochemical conclusions or novel medical interventions. These limited and inconclusive data resulted in no new clear treatment directions for natural therapeutics to treat RP.

More recent data regarding the biochemical pathogenesis of RP is leading to a better understanding of the disease, and interventional investigations have broadened the therapeutic options for patients with RP. In a mouse model of RP, an imbalance between the superoxide dismutase and glutathione peroxidase 4 antioxidant systems was identified in RP.11,12 It has been known for more than a decade that an association between glutathione synthase deficiency and RP exists as well.13 Mitochondrial DNA dysfunction has also been documented in RP, with the following conclusion: “Antioxidant therapies hold promise for improving mitochondrial performance; however, medicine still has large gaps in its knowledge of which types and ratios of antioxidants, and in which forms, will result in the best outcomes. However, physicians seeking systematic treatments for their patients might consider testing urinary organic acids to determine how best to treat them.”14(p90) Given the known imbalance between superoxide dismutase and glutathione peroxidase 4, the low levels of glutathione synthase, and the reported negative effect to vitamin E supplementation, patients with RP may benefit from an approach to balance glutathione production and activity, along with protection of mitochondria.

Therapeutic Interventions to Treat RP

Table 1 lists natural therapeutics to treat RP. Data sources for the research on these agents are also given.

Table 1. Therapeutic Interventions to Treat Retinitis Pigmentosa

Therapeutic AgentDosageSource
Retinol (as vitamin A palmitate)10 000-15 000 IU/dBerson et al,4 1993; Berson,5 2000; Aleman et al,6 2001; Berson,7 2004; Gong et al,8 1992; Bazan et al,9 1986; Berson et al,15 2010
Lutein10-20 mg/dBerson et al,4 1993; Berson,5 2000; Aleman et al,6 2001; Berson,7 2004; Gong et al,8 1992; Bazan et al,9 1986; Berson et al,15 2010
Zeaxanthin10-20 mg/dMiranda et al,16 2010
Docosahexaenoic acid200 mg/d or a diet integrating a mean of 200 mg/d of omega-3–containing fishBerson et al,4 1993; Berson,5 2000; Aleman et al,6 2001; Berson,7 2004; Gong et al,8 1992; Bazan et al,9 1986; Berson et al,17 2012
Glutathione support
  N-acetylcysteine500-600 mg twice dailyLee et al,18 2011; Gibson et al,19 2011
  Alpha lipoic acid200-300 mg twice dailyKomeima et al,20 2006; Miranda et al,16 2010; Bunin et al,21 1992
Magnesium, pantothenic acid, selenium, riboflavin, niacinamideSupport nutrients to balance glutathione cycling and improve intracellular glutathione activityBarbagallo et al,22 1999; Bede et al,23 2008; Zhu et al,24 1993

 

Intravenous glutathione can be of incredible benefit to patients in need of this support and has been shown to increase intercellular magnesium,22 in addition to bolstering circulating glutathione levels. If trained to perform intravenous therapy, physicians can administer intravenous glutathione 1 to 3 times weekly until levels are restored or therapeutic benefit is achieved. An ongoing investigational trial25 at the Bastyr Integrative Oncology Research Center (Bastyr University, Kenmore, Washington) and at Anderson Medical Specialty Associates (Seattle, Washington) is evaluating the administration of intravenous glutathione and support nutrients to optimize glutathione activity in patients with nerve injury. The glutathione preload has a total volume of 635 mL and an osmolarity of 615 mOsm/L; the prescription formula is listed in Table 2. Preliminary data show benefit in the resolution of radiation therapy–induced and chemotherapy-induced neuropathy, likely rendering this formula beneficial in the improvement of glutathione function and activity in nervous system tissues.

Table 2. Glutathione Preload Intravenous Formulaa

Therapeutic AgentDosageVolume, mL
Sterile waterFor infusion500
Vitamin C-50025 g50
Calcium gluconateb1 g10
Magnesium sulfatec2 g4
Zinc chloride25 mg5
Seleniumd400 µg10
Vitamin B-100Multiple-component additivee3
Vitamin B5500 mg2
Vitamin B6100 mg2
Bicarbonate sodiumf8.4%25
Taurine250 mg5

aFrom Anderson and Standish.25 For additions and subtractions, follow with 2 to 4 g of glutathione in 100 mL of normal saline.

bMay substitute 3 mL of calcium chloride.

cMay substitute 10 mL of magnesium chloride.

dMay add 5 to10 mg of methyl vitamin B12.

eVitamin B-100 contains thiamine hydrochloride (100 mg), dexpanthenol (2 mg), riboflavin 5′-phosphate sodium (2 mg), niacinamide (100 mg), and pyridoxine hydrochloride (2 mg).

fOmit in central line.

 

Safe and Efficacious Level of Intervention

While RP has no known cure, data and clinical practice support the use of certain nutrient therapies that enhance the retina and the nervous system. A focus on correcting endogenous imbalance in antioxidant function by maximizing glutathione activity, providing retinal flavonoid support, and enhancing the balance of retinol and omega-3 can provide a safe and efficacious level of intervention.


Paul S. Anderson, ND is a graduate of National College of Natural Medicine, Portland, Oregon, and practices in Seattle, Washington, at Anderson Medical Specialty Associates and the Bastyr Clinical Research Center. He is a cancer researcher at Bastyr University, and his investigations concentrate on intravenous therapies and their influences on cancer and chronic disease. Dr Anderson also teaches board reviews for the Naturopathic Physicians Licensing Examinations, as well as many continuing medical education classes for physicians, including some courses offered through International IV Nutritional Therapy for Professionals, Cedar Ridge, California.

References

1. Medscape. Retinitis pigmentosa. http://emedicine.medscape.com/article/1227488-overview. Accessed July 15, 2012.

2. Haim M. Epidemiology of retinitis pigmentosa in Denmark. Acta Ophthalmol Scand Suppl. 2002;(233):1-34.

3. Boughman JA. Population genetic studies of retinitis pigmentosa. Am J Hum Genet. 1980;32(2):223-235.

4. Berson EL, Rosner B, Sandberg MA, et al. A randomized trial of vitamin A and vitamin E supplementation for retinitis pigmentosa. Arch Ophthalmol. 1993;111(6):761-772.

5. Berson EL. Nutrition and retinal degenerations. Int Ophthalmol Clin. 2000;40(4):93-111.

6. Aleman TS, Duncan JL, Bieber ML, et al. Macular pigment and lutein supplementation in retinitis pigmentosa and Usher syndrome. Invest Ophthalmol Vis Sci. 2001;42(8):1873-1881.

7. Berson E. Further evaluation of docosahexaenoate in patients with retinitis pigmentosa receiving vitamin A treatment: subgroup analysis. Arch Ophthalmol. 2004;122(9):1306-1314.

8. Gong J, Rosner B, Rees DG, et al. Plasma docosahexaenoate levels in various genetic forms of retinitis pigmentosa. Invest Ophthalmol Vis Sci. 1992;33(9):2596-2602.

9. Bazan NG, Scott BL, Reddy TS, Pelias MZ. Decreased content of docosahexaenoate and arachidonate in plasma phospholipids in Usher’s syndrome. Biochem Biophys Res Commun. 1986;141(2):600-604.

10. Arshinoff SA, McCulloch JC, Macrae W, et al. Amino acids in retinitis pigmentosa. Br J Ophthalmol. 1981;65:626-630.

11. Usui S, Oveson BC, Iwase T, et al. Overexpression of SOD in retina: need for increase in H2O2-detoxifying enzyme in same cellular compartment. Free Radic Biol Med. 2011;51(7):1347-1354.

12. Lu L, Oveson BC, Jo YJ, et al. Increased expression of glutathione peroxidase 4 strongly protects retina from oxidative damage. Antioxid Redox Signal. 2009;11(4):715-724.

13. MedLink. Glutathione synthetase deficiency. http://www.medlink.com/medlinkcontent.asp. Accessed July 15, 2012.

14. Pieczenik SR, Neustadt J. Mitochondrial dysfunction and molecular pathways of disease. Exp Mol Pathol. 2007;83(1):84-92.

15. Berson EL, Rosner B, Sandberg MA, et al. Clinical trial of lutein in patients with retinitis pigmentosa receiving vitamin A. Arch Ophthalmol. 2010;128(4):403-495.

16. Miranda M, Alvarez-Nölting R, Araiz J, Romero Gómez FJ. Antioxidant therapy in retinitis pigmentosa. In: Romero Gómez FJ, Miranda M, Soria JM, eds. Novel Aspects of Neuroprotection, 2010. http://www.ehu.es/OftalmoBiologiaExperimental/documentos/antioxidant-therapy-in-retinitis-pigmentosa.pdf. Accessed July 28, 2012.

17. Berson EL, Rosner B, Sandberg MA, Weigel-Difranco C, Willett WC. ù-3 Intake and visual acuity in patients with retinitis pigmentosa receiving vitamin A. Arch Ophthalmol. 2012;130(6):707-711.

18. Lee SY, Usui S, Zafar AB, et al. N-acetylcysteine promotes long-term survival of cones in a model of retinitis pigmentosa. J Cell Physiol. 2011;226(7):1843-1849.

19. Gibson KR, Winterburn TJ, Barrett F, Sharma S, MacRury SM, Megson IL. Therapeutic potential of N-acetylcysteine as an antiplatelet agent in patients with type-2 diabetes. Cardiovasc Diabetol. 2011;10:e43. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3120650/?tool=pubmed. Accessed July 28, 2012.

20. Komeima K, Rogers BS, Lu L, Campochiaro PA. Antioxidants reduce cone cell death in a model of retinitis pigmentosa. Proc Natl Acad Sci U S A. 2006;103(30):11300-11305.

21. Bunin A, Filina AA, Erichev VP, et al. A glutathione deficiency in open-angle glaucoma and the approaches to its correction [in Russian]. Vestn Oftalmol. 1992;108(4-6):13-15.

22. Barbagallo M, Dominguez LJ, Tagliamonte MR, Resnick LM, Paolisso G. Effects of glutathione on red blood cell intracellular magnesium: relation to glucose metabolism. Hypertension. 1999;34(1):76-82.

23. Bede O, Nagy D, Surányi A, Horváth I, Szlávik M, Gyurkovits K. Effects of magnesium supplementation on the glutathione redox system in atopic asthmatic children. Inflamm Res. 2008;57(6):279-286.

24. Zhu Z, Kimura M, Itokawa Y. Selenium concentration and glutathione peroxidase activity in selenium and magnesium deficient rats. Biol Trace Elem Res. 1993;37(2-3):209-217.

25. Anderson P, Standish L. IV therapy experience at Bastyr Integrative Oncology Research Center: ongoing clinical trial involving intravenous therapeutics in cancer and chronic disease; 2012; Seattle, Washington.

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