Biochemistry of vision, Wald cycle, transducin cycle.

Introduction

Vision is initiated when light is absorbed by photoreceptor cells in the retina. This process involves phototransduction, where light is converted into electrical signals. The biochemical basis of this process includes the Wald visual cycle (retinoid cycle) and the transducin signaling pathway. Together, they allow photoreceptors to respond to light and then regenerate their sensitivity for continuous visual function.

Wald Cycle (Visual Cycle)

The Wald cycle describes the biochemical recycling of retinal (a vitamin A derivative) between the photoreceptor cells and retinal pigment epithelium (RPE):

- **In rods**, the light-sensitive pigment is **rhodopsin**, composed of opsin and **11-cis-retinal**.

- **Photon absorption** converts 11-cis-retinal to **all-trans-retinal**, triggering rhodopsin activation.

- All-trans-retinal is released from opsin and reduced to **all-trans-retinol**.

- It is transported to the RPE, where it is converted back to **11-cis-retinal** through a series of enzymatic steps.

- 11-cis-retinal is then returned to photoreceptors to regenerate rhodopsin.

This cycle allows photoreceptors to maintain light sensitivity and adapt to changing light conditions.

Transducin Cycle (Phototransduction Pathway)

Phototransduction refers to the cascade of molecular events initiated by activated rhodopsin in rod cells. It involves a G-protein–coupled pathway centered around transducin:

- Activated rhodopsin (R*) stimulates **transducin (Gt)** by facilitating GDP-GTP exchange on its α-subunit.

- Transducin-GTP activates **cGMP phosphodiesterase (PDE6)**.

- PDE6 hydrolyzes cGMP to GMP → **reduces intracellular cGMP levels**.

- This leads to **closure of cGMP-gated Na⁺/Ca²⁺ channels**, causing hyperpolarization of the photoreceptor membrane.

- The hyperpolarization signal is transmitted to bipolar cells and onward through the visual pathway.

- Inactivation of the signal involves rhodopsin phosphorylation, arrestin binding, and GTP hydrolysis on transducin.

Clinical Relevance

- **Vitamin A deficiency** can impair retinal production and lead to night blindness.

- Mutations in genes involved in the visual or transducin cycle can cause **retinitis pigmentosa** or **Leber congenital amaurosis**.

- Understanding these cycles is essential in developing treatments for retinal degenerative diseases and visual impairments.

Conclusion

The biochemistry of vision involves the transformation of light into electrical signals via the Wald cycle and the transducin pathway. These tightly coordinated cycles ensure continued visual sensitivity and signal transmission in photoreceptors.

References

1. Lehninger Principles of Biochemistry, 7th Edition

2. Lippincott Illustrated Reviews: Biochemistry, 7th Edition

3. Guyton and Hall Textbook of Medical Physiology, 14th Edition