A Curry Spice May Cure Some Forms of Retinitis Pigmentosa
Turmeric is a versatile spice. This yellow orange root is used to flavor curry, dye food and clothing, and has been an ancient Asian remedy for many ailments (see Figure 1). Recently, a group of National Eye Institute-funded researchers found that curcumin, the active ingredient in turmeric, may also be effective in treating the blinding disease retinitis pigmentosa.
Figure 1: Curcumin is the active ingredient in turmeric, a yellow orange root that is dried and ground into powder used to spice curry.
Courtesy of the NEI.
Affecting more than 1 in 4,000 people worldwide, retinitis pigmentosa (RP) is an untreatable disease that leads to severe vision loss and blindness. RP is a group of hereditary degenerative diseases caused by mutations in over 45 different genes. Current experimental treatments with gene transfer involve injecting healthy copies of the mutant gene into the eyes of patients. Although early clinical trials are promising, this approach is expensive and requires developing a treatment for every mutant gene that causes the disease. Now, with the publication of a study led by Radha Ayyagari, Ph.D., associate professor of ophthalmology at the University of California San Diego, doctors may look to curcumin as a simpler way to treat some common forms of RP.
"In my opinion the most advantageous way to treat RP is by identifying a molecule that can be used to treat multiple causes of the disease," Dr. Ayyagari explained.
The changes that cause RP destroy light-detecting photoreceptor cells called rods and cones (see Figure 2), which are located in the retina, the part of the eye that converts light into electrical signals sent to the brain. About 10% of RP cases are caused by mutations in the gene that encodes rhodopsin, a protein rod cells use to detect light. Many of these mutations, such as one called P23H, cause rhodopsin to abnormally cluster inside of rod cells, which impairs rod cell function and ultimately leads to cell death.
Figure 2: After entering the eye, light shines through the retina to the photoreceptor layer where it is detected by rod and cone cells. RP destroys the rod and cone photoreceptor cells.
Courtesy of the NEI and Washington University School of Medicine Neuroscience Tutorial, St. Louis, MO.
Previous studies suggested that curcumin may be an effective treatment for other neurodegenerative diseases caused by abnormal protein clustering. Specifically, a couple of studies showed that curcumin inhibited the formation of amyloid ß plaques, the protein clusters thought to destroy neurons in Alzheimerís disease.
In initial experiments performed by Dr. Ayyagari and her colleagues, curcumin prevented mutant P23H rhodopsin from abnormally clustering in cultured cells grown in petri dishes.
Having grown up in India, where turmeric is traditionally used to treat wounds and inflammations and where she studied nutritional biochemistry at the National Institute of Nutrition, Dr. Ayyagari has a strong appreciation for curcuminís therapeutic potential.
"Coming from India I have a lot of faith in curcumin," Dr. Ayyagari explained.
To test this idea further, the researchers fed curcumin to rats genetically engineered to have the P23H mutation in rhodopsin. Previous studies showed that these rats have eye problems reminiscent of RP. Specifically, the eyes of these rats have poor electrical responses to light and over time, the retina thins with the loss of photoreceptor cells.
Feeding curcumin to the P23H rats alleviated these problems. Curcumin preserved the number of rods and cones in the retina (see Figure 3) and it increased the light-induced electrical response recorded from the ratsí eyes. These results suggest that curcumin may alleviate eye problems by preventing the loss of photoreceptors caused by the P23H mutation.
Figure 3: Retinas, from RP rats fed curcumin (right-hand image) were thicker than retinas of rats not fed curcumin (left-hand image). Some thickening was caused by preservation of rods and cones located in the outer nuclear layer (ONL; white arrow) of the retina.
Courtesy of Dr. Ayyagari, UCSD.
Interestingly, feeding curcumin to the rats caused rods to produce more rhodopsin and cones to produce more of S- and M- opsin, the proteins cones use to detect light. These results further support the idea that curcumin may preserve rod and cone cell function in retinas of patients who have RP caused by mutant P23H rhodopsin.
The P23H mutation causes rhodopsin to accumulate in the endoplasmic reticulum (ER), a maze of membranes located near a cellís nucleus where new proteins are made. Rhodopsin is normally found in the outer segments of rod cells, where it captures light. The researchers looked at the location of the mutant P23H rhodopsin in rod cells by staining retinas from the engineered rats with antibodies that detect rhodopsin. As expected, rhodopsin was abnormally clustered near the nuclei of rod cells from rats that were not fed curcumin (see Figure 4). In contrast, rhodopsin was found in the outer segments of rats fed curcumin, suggesting curcumin preserved normal rhodopsin clustering.
Abnormal protein accumulation in the ER can stress cells, in general. In response, cells often turn on, or express, genes that at first may free the accumulating proteins from the ER but later may instruct the cells to die.
Experiments performed on cultured cells showed that curcumin prevented the expression of two stress genes, called immunoglobulin-binding protein (BiP/Grp78) and C/EBP-homologous protein (CHOP), which was induced when P23H rhodopsin accumulated in the ER. When the researchers looked at retinas from the engineered rats they found that feeding them curcumin prevented the expression of the BiP/Grp78 gene in rod cells but not of the CHOP gene. Although further work is needed, these results suggest that curcumin may partially prevent stress responses in rods.
Figure 4: Curcumin prevents abnormal clustering of mutant rhodopsin. Retinas from RP rats were stained with antibodies that detect rhodopsin (red) and with DAPI, a chemical that stains cell nuclei (blue). Mutant rhodopsin abnormally clustered near rod cell nuclei (left-hand image). Feeding curcumin to RP rats preserved the normal location of rhodopsin clusters to the outer segment (OS) of rods (right-hand image). Courtesy of Dr. Ayyagari, UCSD.
Delivering drugs to the retina is often hindered by the blood-retina barrier, a protective meshwork of cells surrounding the retina which prevents many compounds and chemicals in the bloodstream from entering the retina. The researchers detected curcumin in the retinas of rats after only two days of feeding, indicating that it passes through the blood-retina barrier. These results suggest that patients with RP could simply take curcumin pills or include turmeric in their diet rather than have a drug or gene surgically injected into their eyes.
Demonstrating its passage through the blood-retina barrier also suggests that curcumin could be used to treat any eye disease caused by abnormal protein clustering. For instance, some mutations associated with RP appear to cause abnormal clustering of other proteins found in rods, such as phosphodiesterase 6 (PDE6), a protein that helps rhodopsin convert light into electrical signals. Abnormal protein clustering may also be associated with eye diseases that affect other cells in the retina. The results reported by Dr. Ayyagari and her colleagues suggest that curcumin could treat all of these cases.
Do her results mean that RP patients should include turmeric in their diet?
"We donít know yet. The amounts used in this study are more than one would get in a normal diet. We need to test the effective dose of curcumin in patients," Dr. Ayyagari replied as she explained the next step in her promising research.
- By Christopher G. Thomas, Ph.D.
- Vasireddy et al. "Rescue of Photoreceptor Degeneration by Curcumin in Transgenic Rats with P23H Rhodopsin Mutation." PLoS ONE, June 2011, vol. 6(6), pp. e21193. PubMed
Last Reviewed: December 2011