Immunological consequences of compromised ocular immune privilege accelerate retinal degeneration in retinitis pigmentosa
Abstract Background Retinitis pigmentosa (RP) is a hereditary retinal disease which leads to visual impairment. The onset and progression of RP has physiological consequences that affects the ocular environment. Some of the key non-genetic factors which hasten the retinal degeneration in RP include...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-10-01
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| Series: | Orphanet Journal of Rare Diseases |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13023-022-02528-x |
| _version_ | 1811336300499828736 |
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| author | K. Varsha Mohan Alaknanda Mishra Abaranjitha Muniyasamy Prakriti Sinha Parul Sahu Ashwani Kesarwani Kshama Jain Perumal Nagarajan Vinod Scaria Manisha Agarwal Naseem S. Akhter Chanda Gupta Pramod Upadhyay |
| author_facet | K. Varsha Mohan Alaknanda Mishra Abaranjitha Muniyasamy Prakriti Sinha Parul Sahu Ashwani Kesarwani Kshama Jain Perumal Nagarajan Vinod Scaria Manisha Agarwal Naseem S. Akhter Chanda Gupta Pramod Upadhyay |
| author_sort | K. Varsha Mohan |
| collection | DOAJ |
| description | Abstract Background Retinitis pigmentosa (RP) is a hereditary retinal disease which leads to visual impairment. The onset and progression of RP has physiological consequences that affects the ocular environment. Some of the key non-genetic factors which hasten the retinal degeneration in RP include oxidative stress, hypoxia and ocular inflammation. In this study, we investigated the status of the ocular immune privilege during retinal degeneration and the effect of ocular immune changes on the peripheral immune system in RP. We assessed the peripheral blood mononuclear cell stimulation by retinal antigens and their immune response status in RP patients. Subsequently, we examined alterations in ocular immune privilege machineries which may contribute to ocular inflammation and disease progression in rd1 mouse model. Results In RP patients, we observed a suppressed anti-inflammatory response to self-retinal antigens, thereby indicating a deviated response to self-antigens. The ocular milieu in rd1 mouse model indicated a significant decrease in immune suppressive ligands and cytokine TGF-B1, and higher pro-inflammatory ocular protein levels. Further, blood–retinal-barrier breakdown due to decrease in the expression of tight junction proteins was observed. The retinal breach potentiated pro-inflammatory peripheral immune activation against retinal antigens and caused infiltration of the peripheral immune cells into the ocular tissue. Conclusions Our studies with RP patients and rd1 mouse model suggest that immunological consequences in RP is a contributing factor in the progression of retinal degeneration. The ocular inflammation in the RP alters the ocular immune privilege mechanisms and peripheral immune response. These aberrations in turn create an auto-reactive immune environment and accelerate retinal degeneration. |
| first_indexed | 2024-04-13T17:37:26Z |
| format | Article |
| id | doaj.art-f434b379cc6343818acff51001d5c769 |
| institution | Directory Open Access Journal |
| issn | 1750-1172 |
| language | English |
| last_indexed | 2024-04-13T17:37:26Z |
| publishDate | 2022-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Orphanet Journal of Rare Diseases |
| spelling | doaj.art-f434b379cc6343818acff51001d5c7692022-12-22T02:37:19ZengBMCOrphanet Journal of Rare Diseases1750-11722022-10-0117111210.1186/s13023-022-02528-xImmunological consequences of compromised ocular immune privilege accelerate retinal degeneration in retinitis pigmentosaK. Varsha Mohan0Alaknanda Mishra1Abaranjitha Muniyasamy2Prakriti Sinha3Parul Sahu4Ashwani Kesarwani5Kshama Jain6Perumal Nagarajan7Vinod Scaria8Manisha Agarwal9Naseem S. Akhter10Chanda Gupta11Pramod Upadhyay12National Institute of ImmunologyNational Institute of ImmunologyNational Institute of ImmunologyNational Institute of ImmunologyNational Institute of ImmunologyNational Institute of ImmunologyNational Institute of ImmunologyNational Institute of ImmunologyCSIR Institute of Genomics and Integrative BiologyDr Shroff’s Charity Eye HospitalDr Shroff’s Charity Eye HospitalDr Shroff’s Charity Eye HospitalNational Institute of ImmunologyAbstract Background Retinitis pigmentosa (RP) is a hereditary retinal disease which leads to visual impairment. The onset and progression of RP has physiological consequences that affects the ocular environment. Some of the key non-genetic factors which hasten the retinal degeneration in RP include oxidative stress, hypoxia and ocular inflammation. In this study, we investigated the status of the ocular immune privilege during retinal degeneration and the effect of ocular immune changes on the peripheral immune system in RP. We assessed the peripheral blood mononuclear cell stimulation by retinal antigens and their immune response status in RP patients. Subsequently, we examined alterations in ocular immune privilege machineries which may contribute to ocular inflammation and disease progression in rd1 mouse model. Results In RP patients, we observed a suppressed anti-inflammatory response to self-retinal antigens, thereby indicating a deviated response to self-antigens. The ocular milieu in rd1 mouse model indicated a significant decrease in immune suppressive ligands and cytokine TGF-B1, and higher pro-inflammatory ocular protein levels. Further, blood–retinal-barrier breakdown due to decrease in the expression of tight junction proteins was observed. The retinal breach potentiated pro-inflammatory peripheral immune activation against retinal antigens and caused infiltration of the peripheral immune cells into the ocular tissue. Conclusions Our studies with RP patients and rd1 mouse model suggest that immunological consequences in RP is a contributing factor in the progression of retinal degeneration. The ocular inflammation in the RP alters the ocular immune privilege mechanisms and peripheral immune response. These aberrations in turn create an auto-reactive immune environment and accelerate retinal degeneration.https://doi.org/10.1186/s13023-022-02528-xRetinitis pigmentosaTight junction protein (TJP)Blood brain barrier (BRB)Immune infiltrationTransforming growth factor—beta 1 (TGF-B1)Retinal Degeneration 1 (rd1) |
| spellingShingle | K. Varsha Mohan Alaknanda Mishra Abaranjitha Muniyasamy Prakriti Sinha Parul Sahu Ashwani Kesarwani Kshama Jain Perumal Nagarajan Vinod Scaria Manisha Agarwal Naseem S. Akhter Chanda Gupta Pramod Upadhyay Immunological consequences of compromised ocular immune privilege accelerate retinal degeneration in retinitis pigmentosa Orphanet Journal of Rare Diseases Retinitis pigmentosa Tight junction protein (TJP) Blood brain barrier (BRB) Immune infiltration Transforming growth factor—beta 1 (TGF-B1) Retinal Degeneration 1 (rd1) |
| title | Immunological consequences of compromised ocular immune privilege accelerate retinal degeneration in retinitis pigmentosa |
| title_full | Immunological consequences of compromised ocular immune privilege accelerate retinal degeneration in retinitis pigmentosa |
| title_fullStr | Immunological consequences of compromised ocular immune privilege accelerate retinal degeneration in retinitis pigmentosa |
| title_full_unstemmed | Immunological consequences of compromised ocular immune privilege accelerate retinal degeneration in retinitis pigmentosa |
| title_short | Immunological consequences of compromised ocular immune privilege accelerate retinal degeneration in retinitis pigmentosa |
| title_sort | immunological consequences of compromised ocular immune privilege accelerate retinal degeneration in retinitis pigmentosa |
| topic | Retinitis pigmentosa Tight junction protein (TJP) Blood brain barrier (BRB) Immune infiltration Transforming growth factor—beta 1 (TGF-B1) Retinal Degeneration 1 (rd1) |
| url | https://doi.org/10.1186/s13023-022-02528-x |
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