Retinitis Pigmentoa Research Paper
Biology 2B03 – Cell Biology November 27, 2011
Retinitis Pigmentosa – Rhodopsin Receptor
Abstract
According to Dryja Ap et. al (1990), A rare disease that causes visual imparity, retinitis pigmentosa, is due to SNP mutations in the rhodopsin receptor. RP varies from the age of onset to its severity of the disease itself. With most cases having a gradual loss of the RPE cells and degradation of the cones and rods photoreceptor cells, nyctalopia and tunnel vision are primary indicators of the disease being present in humans. The rhodopsin mutation consists of a G-T nucleotide substitution at the 152nd position in the amino acid chain. Rhodopsin receptor is a member of the largest G-protein coupled receptors (GPCR), which is more commonly referred to Family A. The mutation causes the protein to misfold, thus resulting in the loss of function for that …show more content…
protein. There are no viable cures to this disease as this disease is inherited through several different ways such as autosomal dominant, autosomal recessive, x-linked and many more (Dryja et. al, 1990). However, there are several therapies and preventive measures that can be taken to reduce or at the least prolong the symptoms related to retinitis pigmentosa (Atwood & Finlay, 1994).
Introduction
The retinal disease of retinitis pigmentosa differs in severity and occurs in multiple stages.
Early stages include nyctalopia and tunnel vision (Bessant et al, n.d.). Advance stages comprise of complete loss of the central vision. As per Atwood and Finlay (1994) Retinitis Pigmentosa, RP, can be detected at different ages, ranging from birth to early adulthood. The latter incidence usually has more severe affects and reaches the advance stage where the patient experiences complete loss of cones and rods photoreceptor cells. Most patients passing through the advance stages undergo gradual atrophy of the RPE, retinal pigment epithelium. In contrast to severe cases, patients in the early stages suffer from the loss of rod photoreceptor cells, which causes night blindness. In milder cases, peripheral vision is diminished to the point where only central vision is visible (Atwood & Finlay, 1994). RP varies in the type of inheritance, where almost half of the cases are autosomal dominant and the rest vary between autosomal recessive, x-linked and sporadic (Bessant et al,
n.d.).
Discussion
Dryja et. al (1990) believe the main cause behind this disease is a genetic mutation in the rhodopsin receptor. The mutation is a substitution where a G is substituted with a T nucleotide at the 152nd position in the rhodopsin gene. The rhodopsin receptor falls under the largest group of G-protein coupled receptors, which is referred to as Family A. The family comprises of short extracellular N-terminus and amino acids that are extremely conserved. In specific, rhodopsin is a receptor, which is activated by light photons, which stimulate a retinal bound in transmembrane pocket (Dryja et al, 1990).
The G-protein coupled receptor along with receptor rhodopsin consists of two primary signal transduction pathways: phosphatidylinositol and cAMP signal pathways (Drummond, 1988). The binding of a ligand causes the conformational change in the GPCR. GPCR are integral membrane proteins, which make it very helpful for interaction with hydrophilic drugs and hormones (Dryja et al, 1990). The mutation occurs in this pathway causing the aforementioned symptoms (Drummond, 1988). Another common mutation that occurs is the substitution of Histidine with Proline at the 23rd position in the amino acid sequence, (Pro23His) (Drummond, 1988).
According to Ramakrishnan and Rao (2011), with the mutation of the rhodopsin receptor in humans, a rare disease occurring every one in 4,000 people is detected. Retinitis pigmentosa is the primary cause of blindness and visual imparities in young adults and adolescents. As aforementioned, this disease is caused as a result of the mutations in the rhodopsin receptor, which in turn causes the death of the rods and cones photoreceptors (Ramakrishnan & Rao, 2011). As seen in Figure 1.0, several amino acid residues are mutated and thus the protein loses it functionality as it is misfolded. The figure below is a representation of 7 transmembrane domains, which are indicated by black boxes.
Figure 1.0
Visual representation of Rhodopsin structure. All green dots represent amino acid residues while the red dots represent mutated amino acid residues with retinitis pigmentosa. (Bessant et. al, n.d.)
In recent studies, a new perception to the problem has been discovered. Dryja et. al (1990) suggest that cell death may be a causation of constant, high rate of signal transduction, which causes the rods to die rather than the previous disposition, which assumed cell death as a consequence of lowering the Ca2+.
The genetic mutation causes nyctalopia, tunnel vision and loss of central vision has no definitive cure in the medical field of research. The first symptom of night blindness is solely caused by cell degradation of the rod photoreceptors and there is no cure for regeneration of the rod photoreceptor cells. It is suggested that certain therapies prolong the natural symptoms associated with retinitis pigmentosa. The primary therapy includes daily high intake of Vitamin A as well as natural exposure to sunlight. The shortcoming of this therapy is that the liver is severely affected with food containing high doses of Vitamin A.
Conclusion
The rhodopsin receptor when mutated misfolds the protein and loses its functionality. This causes rods and photoreceptor cells to die which leads to blindness (Ramakrishnan & Rao, 2011). The substitution mutation on 152nd gene on the rhodopsin receptor is the main cause of this disease where a G-T nucleotide substitution happens (Atwood et. al, 1994). Even though, there are no cures that eliminate the diseases, several therapies can be induced to the patient, which relieves the severity of the symptoms (Drummond, 1988). Even through you can prolong the symptoms, the patient will eventually suffer from night blindness and tunnel vision eventually (Atwood et. al, 1994).
References
Attwood, T.K. and J.B. Findlay, 1994. Fingerprinting G-protein-coupled receptors. Protein Eng., 7: 195-203.
Bessant DA, Payne AM, Mitton KP, Wang QL, Swain PK, Plant C, et al. A mutation in NRL is associated with autosomal dominant retinitis pigmentosa. Nat Genet 1999;21:355-6.
D. Ramakrishna and P. Rao, 2011. Applications of G Protein-coupled Receptors in Clinical Medicine. Current Research in Neuroscience, 1: 15-23.
Drummond, A.H., 1988. Lithium affects G-protein receptor coupling. Nature, 331: 388-388.
Dryja TP, McGee TL, Reichel E, Hahn LB, Cowley GS, Yandell DW, et al. A point mutation of the rhodopsin gene in one form of retinitis pigmentosa. Nature 1990; 343:364-6
Retinitis Pigmentosa – Rhodopsin Receptor
Abstract
According to Dryja Ap et. al (1990), A rare disease that causes visual imparity, retinitis pigmentosa, is due to SNP mutations in the rhodopsin receptor. RP varies from the age of onset to its severity of the disease itself. With most cases having a gradual loss of the RPE cells and degradation of the cones and rods photoreceptor cells, nyctalopia and tunnel vision are primary indicators of the disease being present in humans. The rhodopsin mutation consists of a G-T nucleotide substitution at the 152nd position in the amino acid chain. Rhodopsin receptor is a member of the largest G-protein coupled receptors (GPCR), which is more commonly referred to Family A. The mutation causes the protein to misfold, thus resulting in the loss of function for that …show more content…
protein. There are no viable cures to this disease as this disease is inherited through several different ways such as autosomal dominant, autosomal recessive, x-linked and many more (Dryja et. al, 1990). However, there are several therapies and preventive measures that can be taken to reduce or at the least prolong the symptoms related to retinitis pigmentosa (Atwood & Finlay, 1994).
Introduction
The retinal disease of retinitis pigmentosa differs in severity and occurs in multiple stages.
Early stages include nyctalopia and tunnel vision (Bessant et al, n.d.). Advance stages comprise of complete loss of the central vision. As per Atwood and Finlay (1994) Retinitis Pigmentosa, RP, can be detected at different ages, ranging from birth to early adulthood. The latter incidence usually has more severe affects and reaches the advance stage where the patient experiences complete loss of cones and rods photoreceptor cells. Most patients passing through the advance stages undergo gradual atrophy of the RPE, retinal pigment epithelium. In contrast to severe cases, patients in the early stages suffer from the loss of rod photoreceptor cells, which causes night blindness. In milder cases, peripheral vision is diminished to the point where only central vision is visible (Atwood & Finlay, 1994). RP varies in the type of inheritance, where almost half of the cases are autosomal dominant and the rest vary between autosomal recessive, x-linked and sporadic (Bessant et al,
n.d.).
Discussion
Dryja et. al (1990) believe the main cause behind this disease is a genetic mutation in the rhodopsin receptor. The mutation is a substitution where a G is substituted with a T nucleotide at the 152nd position in the rhodopsin gene. The rhodopsin receptor falls under the largest group of G-protein coupled receptors, which is referred to as Family A. The family comprises of short extracellular N-terminus and amino acids that are extremely conserved. In specific, rhodopsin is a receptor, which is activated by light photons, which stimulate a retinal bound in transmembrane pocket (Dryja et al, 1990).
The G-protein coupled receptor along with receptor rhodopsin consists of two primary signal transduction pathways: phosphatidylinositol and cAMP signal pathways (Drummond, 1988). The binding of a ligand causes the conformational change in the GPCR. GPCR are integral membrane proteins, which make it very helpful for interaction with hydrophilic drugs and hormones (Dryja et al, 1990). The mutation occurs in this pathway causing the aforementioned symptoms (Drummond, 1988). Another common mutation that occurs is the substitution of Histidine with Proline at the 23rd position in the amino acid sequence, (Pro23His) (Drummond, 1988).
According to Ramakrishnan and Rao (2011), with the mutation of the rhodopsin receptor in humans, a rare disease occurring every one in 4,000 people is detected. Retinitis pigmentosa is the primary cause of blindness and visual imparities in young adults and adolescents. As aforementioned, this disease is caused as a result of the mutations in the rhodopsin receptor, which in turn causes the death of the rods and cones photoreceptors (Ramakrishnan & Rao, 2011). As seen in Figure 1.0, several amino acid residues are mutated and thus the protein loses it functionality as it is misfolded. The figure below is a representation of 7 transmembrane domains, which are indicated by black boxes.
Figure 1.0
Visual representation of Rhodopsin structure. All green dots represent amino acid residues while the red dots represent mutated amino acid residues with retinitis pigmentosa. (Bessant et. al, n.d.)
In recent studies, a new perception to the problem has been discovered. Dryja et. al (1990) suggest that cell death may be a causation of constant, high rate of signal transduction, which causes the rods to die rather than the previous disposition, which assumed cell death as a consequence of lowering the Ca2+.
The genetic mutation causes nyctalopia, tunnel vision and loss of central vision has no definitive cure in the medical field of research. The first symptom of night blindness is solely caused by cell degradation of the rod photoreceptors and there is no cure for regeneration of the rod photoreceptor cells. It is suggested that certain therapies prolong the natural symptoms associated with retinitis pigmentosa. The primary therapy includes daily high intake of Vitamin A as well as natural exposure to sunlight. The shortcoming of this therapy is that the liver is severely affected with food containing high doses of Vitamin A.
Conclusion
The rhodopsin receptor when mutated misfolds the protein and loses its functionality. This causes rods and photoreceptor cells to die which leads to blindness (Ramakrishnan & Rao, 2011). The substitution mutation on 152nd gene on the rhodopsin receptor is the main cause of this disease where a G-T nucleotide substitution happens (Atwood et. al, 1994). Even though, there are no cures that eliminate the diseases, several therapies can be induced to the patient, which relieves the severity of the symptoms (Drummond, 1988). Even through you can prolong the symptoms, the patient will eventually suffer from night blindness and tunnel vision eventually (Atwood et. al, 1994).
References
Attwood, T.K. and J.B. Findlay, 1994. Fingerprinting G-protein-coupled receptors. Protein Eng., 7: 195-203.
Bessant DA, Payne AM, Mitton KP, Wang QL, Swain PK, Plant C, et al. A mutation in NRL is associated with autosomal dominant retinitis pigmentosa. Nat Genet 1999;21:355-6.
D. Ramakrishna and P. Rao, 2011. Applications of G Protein-coupled Receptors in Clinical Medicine. Current Research in Neuroscience, 1: 15-23.
Drummond, A.H., 1988. Lithium affects G-protein receptor coupling. Nature, 331: 388-388.
Dryja TP, McGee TL, Reichel E, Hahn LB, Cowley GS, Yandell DW, et al. A point mutation of the rhodopsin gene in one form of retinitis pigmentosa. Nature 1990; 343:364-6