Retinitis pigmentosa (RP) refers to a group of inherited diseases causing retinal degeneration. The cell-rich retina lines the back inside wall of the eye. It is responsible for capturing images from the visual field. People with RP experience a gradual decline in their vision because photoreceptor cells (rods and cones) die. Forms of RP and related diseases include Ushers syndrome, Leber’s congenital amaurosis, rod-cone disease, Bardet-Biedl syndrome, and Refsum disease, among others. Symptoms depend on whether rods or cones are initially involved. In most forms of RP, rods are affected first. Because rods are concentrated in the outer portions of the retina and are triggered by dim light, their degeneration affects peripheral and night vision. When the more centrally located cones - responsible for color and sharp central vision - become involved, the loss is in color perception and central vision.

Night blindness is one of the earliest and most frequent symptoms of RP. People with mainly cone degeneration, however, first experience decreased central vision and ability to discriminate color.

RP is typically diagnosed in adolescents and young adults. It is a progressive disorder. The rate of progression and degree of visual loss varies from person to person. Most people with RP are legally blind by age 40, with a central visual field of less than 20 degrees in diameter. In families with X-linked RP, males are more often and more severely affected; females carry the genetic trait and experience vision loss less frequently.


The National Eye Institute (NEI) estimates that approximately 100,000 people in the United States have RP. About 2.2 million people are afflicted worldwide. RP is a severe disease and has no current effective treatment.1


Accumulating experimental evidence has shown that oxidative stress is a pathogenic factor in RP (Komeima et al., 2006 2; Komeima et al., 2007 3; Tuson et al., 2009 4; Usui et al., 2009a 5, Usui et al., 2009b 6). In a study using the rd1 mouse model of RP, a mixture of antioxidants including alpha-tocopherol, ascorbic acid, Mn(III)tetrakis(4 benzoic acid)porphyrin and alpha-lipoic acid improved biomarkers of oxidative stress (protein carbonyl adducts and acrolein staining) and partially preserved cone function. (Komeima et al. 2006).

In a study of RP patients, Campochiaro et al. (2015) 7 reported a significant reduction in the ratio of reduced glutathione (GSH) to oxidized glutathione (GSSG) in aqueous humor, and a significant increase in aqueous protein carbonyl content, compared to control subjects. In contrast, there was no significant decrease in the serum GSH/GSSG ratio or increase in carbonyl content of serum proteins. These data suggest that patients with RP have ocular oxidative stress and that oxidative damage-induced cone cell death in animal models of RP may translate to human RP. These observations lead to the hypothesis that potent antioxidants should promote cone survival and function in patients with RP and that the aqueous GSH/GSSG ratio and protein carbonyl content may provide useful biomarkers.

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In a published study measuring Photopic B-Waves, which are generated by cone photoreceptors, the data demonstrated that orally administered NACA preserved cone function in an animal model of RP.


N-acetyl-L-cysteine (NAC) is a well-known, endogenous antioxidant moiety that is capable of facilitating glutathione biosynthesis and replenishing glutathione within cells that are undergoing oxidative stress. It is also FDA-approved for the treatment of acetaminophen overdose and as a mucolytic.


N-acetylcysteine amide (NACA) is the amide form of NAC. It is more lypophilic and more easily permeates cell membranes than NAC. In animal studies with mice it has shown great potential for crossing the blood-brain and retinal barriers.


The use of NAC and NACA for the treatment of RP was initially investigated by Dr. Peter Campochiaro, George S. & Dolores Doré Eccles Professor of Ophthalmology & Neuroscience, Wilmer Eye Institute, The Johns Hopkins School of Medicine. Dr. Campochiaro, a renowned expert in retinal degeneration, advises Nacuity regarding its clinical science program.

Campochiaro’s Group (Lee et al., 2011) 8 demonstrated that orally administered NAC reduced cone cell death and preserved cone function by reducing oxidative damage in two models of RP, rd1+/+ and rd10+/+ mice. In rd10+/+ mice, supplementation of drinking water with NAC promoted partial maintenance of cone structure and function for at least 6 months. Furthermore, Campochiaro’s Group (Dong et al., 2014) 9 compared NAC with NACA in an animal model of RP. Starting at postnatal day (P) 14, rd10+/+ mice were given normal drinking water (controls, n=6) or water containing either 7mg/ml NACA or 20mg/ml NAC (n=8 for each group). Scotopic and photopic electroretinograms (ERGs) were recorded at P14, P35 and P50. Cone density was measured at P50 in four 230 mm x 230 mm (512 x 512 pixels) areas located 0.5mm superior, temporal, inferior, and nasal to the center of the optic nerve in retinal flat mounts stained with fluorescein-labeled peanut agglutinin (PNA). At P35, mean peak scotopic ERG b-wave amplitude was similar in rd10+/+ mice treated with 7mg/ml NACA or 20mg/ml NAC, and significantly greater (about 2-fold) than controls. Mean peak photopic b-wave amplitude was 41% higher (p=0.024) in NACA-treated mice than NAC-treated mice and both were more than 3-fold higher than that in controls. At P50, mean peak scotopic ERG b-wave amplitude was more than 5-fold higher in NAC- or NACA-treated mice than in controls with mean b-wave amplitudes significantly greater in NACA-treated mice compared with NAC-treated mice at 10 of 11 stimulus intensities. Mean photopic ERG b-wave amplitude was 50% higher (p=0.001) at all 3 stimulus intensities in NACA-treated versus NAC-treated mice and more than 4-fold greater than controls. At P50, cone cell density was significantly greater in 3 of 4 quadrants in NACA-treated mice compared to NAC-treated mice. Even with a substantially lower oral dose, NACA exhibited significantly greater preservation of cone cell function and cone survival compared with NAC in rd10+/+ mice.


Nacuity has successfully completed a Phase I Clinical Trial in healthy volunteers. Planning is underway for a Phase II Clinical Trial in patients.


  1. "Facts About Retinitis Pigmentosa", NEI Website
  2. Komeima K, Rogers BS, Lu L, Campochiaro PA. Antioxidants reduce cone cell death in a model of retinitis pigmentosa. Proc Natl Acad Sci USA 2006; 103: 11300-11305.
  3. Komeima K, Rogers BS, Campochiaro PA. Antioxidants slow photoreceptor cell death in mouse models of retinitis pigmentosa. J Cell Physiol 2007; 213:809-815.
  4. Tuson M, Garanto A, Gonzalez-Duarte R, Marfany G. Over-expression of CERKL, a gene responsible for retinitis pigmentosa in humans, protects cells from apoptosis induced by oxidative stress. Molec Vis [serial online] 2009; 15:168-180.
  5. Usui S, Komeima K, Lee SY, et al. Increased expression of catalase and superoxide dismutase 2 reduces cone cell death in retinitis pigmentosa. Mol Ther 2009a; 17(5):778-786.
  6. Usui S, Overson BC, Lee SY, et al. NADPH oxidase plays a central role in cone cell death in retinitis pigmentosa. J Neurochem 2009b; 110: 1028-1037.
  7. Campochiaro PA, Strauss R, Lu L, Hafiz G, Wolfson Y, Shah SM, Sophie R, Mir TA and Scholl HP. Is there excess oxidative stress and damage in eyes of patients with retinitis pigmentosa? Antiox and Redox Signal, 23: 643- 647.
  8. Lee SY, Usui S, Zafar A-B, Oveson BD, Jo, Y-J, Lu L, Masoudi S, Campochiaro PA. N-AcetyIcysteine promotes long-term survival of cones in a model of retinitis pigimentosa. J Cell Physiol 2011; 226; 1843-1849.
  9. Dong A; Stevens R; Hackett S; Campochiaro PA. Compared with N-acetylcysteine (NAC), N-Acetylcysteine Amide (NACA) Provides Increased Protection of Cone Function in a Model of Retinitis Pigmentosa. Investigative Ophthalmology & Visual Science April 2014, Vol.55, 1736.