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A Glimpse of Gold: Oguchi’s Disease and Night Vision Puzzle

by | May 1, 2025 | Manuscripts | 0 comments

Drishti Baisla, B.Optom. Student1

Roshni Sengupta, Assistant Professor2

GD Goenka University, Gurugram, India

 

Oguchi’s disease is a rare autosomal recessive form of congenital stationary night blindness caused by defects in the inactivation process of rod phototransduction. (1) A hallmark feature of this condition is the Mizuo–Nakamura phenomenon, characterised by a light-dependent golden sheen of the fundus that disappears after prolonged dark adaptation. (2,3) First described in 1907 by Dr. Chuta Oguchi, this disorder has been reported more frequently in the Japanese population compared to others.(4) Clinically, patients typically present with normal visual acuity, intact visual fields, and normal colour vision, despite significant night vision impairment. Diagnosis is confirmed through genetic testing, with two primary genes implicated: SAG (S-antigen; OMIM: 181031) and GRK1 (G-protein-dependent receptor kinase 1; OMIM: 180381).(2,3,5,6) Both males and females have an equal chance of inheriting the condition if they receive two copies of the defective gene and consanguinity marriage also significantly increases the likelihood of this inheritance pattern.(7)

The Golden Sheen Phenomenon: A Signature of Oguchi Disease

A striking feature of Oguchi disease is the golden-yellow or orange sheen observed on the fundus after prolonged dark adaptation. This phenomenon is believed to result from the accumulation of a retinoid-like substance in the photoreceptor layer. The sheen disappears upon light exposure and gradually returns when the patient remains in darkness for an extended period. (8) The slow regeneration of rhodopsin further contributes to this unique visual effect.

Distinctive Features of Oguchi Disease

  • A Rare Condition – A bilateral, congenital, and stationary disorder with a hereditary pattern.
  • Chameleon-like Fundus Changes – The “golden sheen” or “golden discoloration” at the posterior pole fades in the dark but reappears within an hour of light exposure.
  • Vascular Anomalies – A washed-out appearance of peripheral retinal vessels and less distinct choroidal vessels.
  • The Light-to-Dark Transition Effect – After about one hour in darkness, the retina appears normal, and vision improves. However, re-exposure to light gradually brings back the golden hue, starting with a spotty pattern that becomes complete within an hour.

Classification- Genetic Basis:

It is classified into two types based on the mutated gene:

Oguchi disease-1: It can result from mutations in the SAG gene, located on chromosome 2q37.1, (3,5,6) which encodes arrestin, a key regulatory protein in the phototransduction cascade. Arrestin binds to activated rhodopsin, preventing its prolonged stimulation. Mutations in this gene impair the timely inactivation of rhodopsin, thereby delaying phototransduction recovery. Additionally, such disruptions have also been associated with the development of retinitis pigmentosa. (9,10,11,12)

Oguchi disease-2: Mutations in the GRK1 gene, located on chromosome 13q34,  (13,14,15,16) are responsible for type 2. GRK1 encodes rhodopsin kinase, an enzyme that plays a critical role in desensitising activated rhodopsin, allowing photoreceptors to reset and respond to new light signals. When mutated, the enzyme’s catalytic activity is reduced, resulting in delayed recovery of photoreceptors.

Disruptions in either GRK1 or SAG result in the accumulation of retinoid substances within the photoreceptors, which is believed to contribute to the distinctive golden sheen observed in Oguchi’s disease. Additionally, based on the distribution pattern of the golden sheen within the retina, Oguchi disease has been classified into five subtypes: entire fundus involvement, macula sparing, posterior fundus sparing, peripheral sparing, and far peripheral sparing. (17)

Mechanism:

The Photo-Transduction Cascade: When photons of visible light strike the eye, they trigger a series of biochemical reactions in photoreceptor cells known as the photo-transduction cascade. While rods and cones share similar pathways, the proteins involved are encoded by distinct genes. In low-light conditions, this visual process is initiated in the outer segments of rod photoreceptors. To date, several genes implicated in congenital stationary night blindness have been found to encode key proteins in the rod photo-transduction cascade, including rhodopsin, the alpha subunit of transducin, the beta subunit of cGMP-phosphodiesterase, arrestin, and rhodopsin kinase. (18)

Rhodopsin and Dominant Stationary night blindness: In the dark-adapted state, the protein opsin, a component of rhodopsin, is covalently bound to 11-cis-retinal, a vitamin A derivative. When a photon of light is absorbed, 11-cis-retinal undergoes a conformational change to all-trans-retinal, triggering structural changes in rhodopsin that activate the molecule. So far, three dominant missense mutations in the rhodopsin gene—Gly90Asp, Thr94Ile, and Ala292Glu—have been identified as being linked to stationary night blindness. Each mutation alters a single amino acid, with two located in rhodopsin’s second transmembrane domain and one in the seventh transmembrane domain. (18)

Conclusion:

A deeper understanding of the underlying mechanisms of Oguchi disease holds promise for the development of future therapeutic interventions in this currently irreversible and progressive blinding condition. Continued research focusing on genetic mutations, especially through the use of animal models and cutting-edge genome-editing technologies, is highly encouraged. Integrating these findings with existing knockout model data may uncover valuable insights into disease progression and aid in formulating targeted treatment strategies.

 

References:

  1. Rishi, P., Rishi, E., & Abraham, S. (2018). Oguchi’s disease with Mizuo-Nakamura phenomenon in a seven-year-old boy. GMS Ophthalmology Cases, 8, Doc07.
  2. Fujinami, K., Tsunoda, K., Nakamura, M., Oguchi, Y., & Miyake, Y. (2011). Oguchi disease with unusual findings associated with a heterozygous mutation in the SAG gene. Archives of Ophthalmology, 129(10), 1375-1376.
  3. Waheed, N. K., Qavi, A. H., Malik, S. N., Maria, M., Riaz, M., Cremers, F. P., … & Qamar, R. (2012). A nonsense mutation in S-antigen (p. Glu306*) causes Oguchi disease. Molecular Vision, 18, 1253.
  4. Oguchi, C. (1907). On a type of night-blindness. Acta Soc Ophthalmol Jpn, 11, 123-134.
  5. Colombo, L., Abeshi, A., Maltese, P. E., Frecer, V., Miertuš, J., Cerra, D., … & Rossetti, L. (2019). Oguchi type I caused by a homozygous missense variation in the SAG gene. European Journal of Medical Genetics, 62(9), 103548.
  6. Maw, M. A., John, S., Jablonka, S., Müller, B., Kumaramanickavel, G. O. V. I. N. D. A. S. A. M. Y., Oehlmann, R., … & Gal, A. (1995). Oguchi disease: suggestion of linkage to markers on chromosome 2q. Journal of medical genetics, 32(5), 396-398.
  7. Singh, D., Singh, D., & Bansal, D. C. (1977). Oguchi′ s disease. Indian Journal of Ophthalmology, 25(1), 1-4.
  8. Deng, Z., Fan, F., Tang, D., Wu, Y., Shu, Y., & Wu, K. (2022). A compound heterozygous mutation in the S-Antigen Visual Arrestin SAG gene in a Chinese patient with Oguchi type one: a case report. BMC ophthalmology, 22(1), 99.
  9. Sonoyama, H., Shinoda, K., Ishigami, C., Tada, Y., Ideta, H., Ideta, R., … & Miyake, Y. (2011). Oguchi disease masked by retinitis pigmentosa. Documenta ophthalmologica, 123, 127-133.
  10. Sullivan, L. S., Bowne, S. J., Koboldt, D. C., Cadena, E. L., Heckenlively, J. R., Branham, K. E., … & Daiger, S. P. (2017). A novel dominant mutation in SAG, the arrestin-1 gene, is a common cause of retinitis pigmentosa in Hispanic families in the Southwestern United States. Investigative ophthalmology & visual science, 58(5), 2774-2784.
  11. Nishiguchi, K. M., Ikeda, Y., Fujita, K., Kunikata, H., Akiho, M., Hashimoto, K., … & Abe, T. (2019). Phenotypic features of Oguchi disease and retinitis pigmentosa in patients with S-antigen mutations: a long-term follow-up study. Ophthalmology, 126(11), 1557-1566.
  12. Nakazawa, M., Wada, Y., & Tamai, M. (1998). Arrestin gene mutations in autosomal recessive retinitis pigmentosa. Archives of ophthalmology, 116(4), 498-501.
  13. Zhang, Q., Zulfiqar, F., Riazuddin, S. A., Xiao, X., Yasmeen, A., Rogan, P. K., … & Hejtmancik, J. F. (2005). A variant form of Oguchi disease mapped to 13q34 associated with partial deletion of GRK1 gene. Mol Vis, 11, 977-985.
  14. Ballios, B. G., Weisbrod, D., Kohly, R., Muni, R. H., Wright, T., & Yan, P. (2020). Wide-field true-colour imaging and clinical characterization of a novel GRK1 mutation in Oguchi disease. Documenta Ophthalmologica, 141, 181-185.
  15. Skorczyk-Werner, A., Kocięcki, J., Wawrocka, A., Wicher, K., & Krawczyński, M. (2015). The first case of Oguchi disease, type 2 in a Polish patient with confirmed GRK1 gene mutation. Klinika Oczna/Acta Ophthalmologica Polonica, 117(1), 27-30.
  16. Teke, M. Y., Citirik, M., Kabacam, S., Demircan, S., & Alikasifoglu, M. (2016). A novel missense mutation of the GRK1 gene in Oguchi disease. Molecular Medicine Reports, 14(4), 3129-3133.
  17. Hashimoto, H., & Kishi, S. (2009). Shortening of the rod outer segment in Oguchi disease. Graefe’s Archive for Clinical and Experimental Ophthalmology, 247, 1561-1563.
  18. Dryja, T. P. (2000). Molecular genetics of Oguchi disease, fundus albipunctatus, and other forms of stationary night blindness: LVII Edward Jackson Memorial Lecture. American journal of ophthalmology, 130(5), 547-563.

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