RP Patients Research Articles

Cone Photoreceptors Develop Normally in the Absence of Functional Rod Photoreceptors in a Transgenic Swine Model of Retinitis Pigmentosa

Human and swine retinas have morphological and functional similarities. In the absence of primate models, the swine is an attractive model to study retinal function and disease, with its cone-rich visual streak, our ability to manipulate their genome, and the differences in susceptibility of rod and cone photoreceptors to disease. We characterized the normal development of cone function and its subsequent decline in a P23H rhodopsin transgenic (TgP23H) miniswine model of autosomal dominant RP. Semen from TgP23H miniswine 53-1 inseminated domestic swine and produced TgP23H and Wt hybrid littermates. Retinal function was evaluated using ERGs between postnatal days (P) 14 and 120. Retinal ganglion cell (RGC) responses were recorded to full-field stimuli at several intensities. Retinal morphology was assessed using light and electron microscopy. Scotopic retinal function matures in Wt pigs up to P60, but never develops in TgP23H pigs. Wt and TgP23H photopic vision matures similarly up to P30 and diverges at P60 where TgP23H cone vision declines. There are fewer TgP23H RGCs with visually evoked responses at all ages and their response to light is compromised. Photoreceptor morphological changes mirror these functional changes. Lack of early scotopic function in TgP23H swine suggests it as a model of an aggressive form of RP. In this mammalian model of RP, normal cone function develops independent of rod function. Therefore, its retina represents a system in which therapies to rescue cones can be developed to prolong photopic visual function in RP patients.

Clinical usefulness of measuring red blood cell distribution width in patients with systemic sclerosis

Red blood cell distribution width (RDW) is a biomarker quantifying the variability of red blood cell size in peripheral blood. Elevated RDW has been found to be an independent prognostic factor for cardiovascular events. SSc is characterized by generalized micro- and macroangiopathy. Our aim was to investigate RDW as a potential biomarker for the assessment of the severity of vascular involvement. One hundred and sixty-eight consecutive SSc patients--62 with dcSSc and 106 with lcSSc--were investigated at baseline and after 1-year of follow-up. Measurements in 93 patients with primary RP and 40 healthy subjects served as controls. The median RDW value of patients with SSc was higher [14.2% (25th-75th percentiles 13.5-14.8%) compared with the group of primary RP patients [13.9% (13.4-14.4%); P < 0.05) and healthy volunteers [13.6% (13.2-13.8%; P < 0.01]. dcSSc and anti-topoisomerase antibody-positive cases showed elevated RDW values compared with lcSSc and anti-topoisomerase antibody-negative cases (P < 0.05). RDW showed a positive correlation with inflammatory markers, including ESR (P < 0.05) and CRP (P < 0.05), and a negative correlation with forced vital capacity (P < 0.05) and diffusing capacity of the lung for carbon monoxide (DLCO) (P < 0.05) during the follow-up. An increase in RDW of >5% during follow-up was associated with an average 8.9% decrease in left ventricular ejection fraction (LVEF) and 7% in DLCO and these associations were independent of each other. RDW in SSc may represent an integrative measure of multiple pathological processes including extensive vasculopathy, fibrosis or ongoing inflammation. An increase in RDW may indicate an impairment of cardiorespiratory function.

Correction of Ureteropelvic Junction Obstruction in Children: National Trends and Comparative Effectiveness in Operative Outcomes

To assess the national trends and comparative effectiveness of the various treatments for pediatric ureteropelvic junction obstruction (UPJO). Within the Nationwide Inpatient Sample, a weighted estimate of 35,275 pediatric patients (<19 years; 1998-2010) with UPJO underwent open pyeloplasty (OP), laparoscopic pyeloplasty (LP), robot-assisted pyeloplasty (RP, ≥October 2008) or endopyelotomy (EP). National trends in utilization and comparative effectiveness were evaluated. Minimally invasive pyeloplasty (RP+LP, MIP) utilization began to increase in 2007; MIP accounted for 16.9% of cases (2008-2010). EP accounted for 1.4% of all cases from 1998 to 2010. On individual multivariate models (relative to OP): (a) no significant differences were noted between groups for intraoperative complications; (b) RP and LP had equivalent risks of postoperative complications developing (vs OP), but EP had a significantly higher risk of postoperative complications; (c) RP and EP had significantly higher risks of necessitating transfusions; (d) RP, LP, and EP had higher overall risks of greater hospital charges; (e) RP had a lower risk of greater length of stay, while EP had a higher risk (LP and OP were equivalent). OP continues to be the predominant treatment for patients with UPJO. RP was the most common MIP modality in every age group. Compared with OP patients, RP patients had equivalent risk for intraoperative and postoperative complications, lower risk for greater length-of-stay, but higher risks for transfusions and greater hospital charges. LP patients had higher overall hospital charges, but no mitigating benefits relative to OP. EP fared poorly on most outcomes.

What is the optimal management of Gleason score 7 (GS7) prostate cancer (PC) at biopsy? A comparison of disease control for prostatectomy (RP) versus radiation therapy (RT).

250 Background: Optimal therapy for Gleason score 7 (GS7) prostate cancer (PC) remains to be defined, with consensus guidelines identifying both prostatectomy (RP) and radiation therapy (RT) as acceptable. The present investigation seeks to compare outcomes between these treatment approaches. Methods: Patients were retrospectively identified for inclusion by clinically localized disease, GS7, and a prostate-specific antigen (PSA) less than 30 at diagnosis. Comparison of demographic, tumor, staging, and outcome variables was performed. Disease recurrence was defined as per contemporary society guidelines. Kaplan-Meier method employed for disease control estimates. Results: Between 2003 and 2010, 267 patients were diagnosed with GS7 prostate cancer, of whom 207 were eligible for the current analysis (120 RP/87 RT). Excepting older age for RT patients (median age 73 vs. 62), the groups were well-balanced. For RP patients, 82 patients (60%) had at least one high-risk feature, of whom only four (5%) received adjuvant RT. For RT patients, 71 of patients (82%) received hormone therapy (median duration 6 months), and 48% (42) underwent external beam RT alone, 41% (36) brachytherapy (BT) alone, and 10% (9) external beam RT plus BT boost. At a median follow-up of 62.2 months (range, 13.1-136.6; with no difference between treatment groups), 64 patients had PSA relapse (51 RP/13 RT) and 15 had died (five of or with disease). Five-year disease-free and disease-specific survivals for RP versus RT were 55.4% versus 82.6% (p&lt;0.0001) and 97.6% versus 98.8% (p=NS), respectively. Conclusions: For GS7 prostate cancer patients, RT is associated with superior disease-free survival at 5 years when compared with RP alone. Whether this difference remains in the setting of appropriately employed adjuvant RT remains to be determined. No difference in survival endpoints was detected, though there were few events at 5 years.

YouTube as a source of information about retinitis pigmentosa

Sir, The internet is an increasingly important health-care resource, providing users with rapid, inexpensive access to medical information. Video streaming websites, such as YouTube, the third most visited website, are the key providers of this information.1, 2 Despite being a major source of health-care information, YouTube is not peer-reviewed and its content is not screened for scientific accuracy prior to being uploaded. The authors sought to categorise videos relating to retinitis pigmentosa on YouTube, both by factual accuracy and by source. The first 10 pages of results generated by searching ‘retinitis pigmentosa' were reviewed (1/6/2012). The sample consisted of 162 videos, which were watched by two independent researchers and categorised as ‘useful', ‘misleading', or ‘no information'. ‘Useful' videos contained scientifically accurate information and/or useful information on social aspects of the illness. ‘Misleading' videos contained scientifically unproven information, such as claims of acupuncture or faith-healing completely restoring vision. ‘No information' videos contained no content relevant to RP. Videos were also classified according to the source; charity, independent user, medical professional, popular media, university, and medical advertisement. We found 82 videos to be misleading; 78 of these were classified as medical advertisements. Only 51 videos provided useful, with scientifically accurate content (Table 1). In total, the videos received over 150 000 views annually. Charities, medical professionals, and universities were the most likely to upload useful videos (Table 2). Videos uploaded by independent users generally focused on the social impact of RP (Table 3). These results differ significantly from previous evaluations of medical content on YouTube, which found that <20% of the videos were misleading.3, 4 These studies employed similar methodology but investigated conditions with established medical treatments. Table 1 Categorisation according to value of content Table 2 Information provided by all videos stratified for source Table 3 Analysis of all useful videos stratified for video source The authors believe the high incidence of misleading videos regarding RP result from the lack of effective medical treatments for the condition. Patients frustrated at the lack of treatment available in the clinic turn to the internet, seeking potential treatments. Unfortunately, YouTube provides an excellent platform for the unregulated advertisement of unproven and often expensive alternative therapies. We therefore recommend that RP patients be directed towards reliable, peer-reviewed information sources and be advised that content on open-access websites is commonly misleading.

Neurological involvement of relapsing polychondritis in Japan: An epidemiological study

We conducted a large scale epidemiological study in Japan and revealed a high mortality rate in RP patients with neurological involvement. Japanese RP patients developed encephalitis/meningitis (12 out of 239 cases, 5.0%), cerebral infarct/bleeding (5 cases, 2.1%) and cerebral vasculitis (4 cases, 1.7%). The mortality rate was 18%, in contrast to 8.1% of RP patients without neurological involvement. We suggested that neurological involvement appeared to be a major determinant of disease severity in patients with RP.

Reduced Port Surgery for Prostate Cancer is Feasible: Comparative Study of 2-port Laparoendoscopic and Conventional 5-port Laparoscopic Radical Prostatectomy

While 5-port laparoendoscopic radical prostatectomy is standard practice, efforts have been focused in developing a single port surgery for cosmetic reasons. However, this is still in the pioneering stage considering the challenging nature of the surgical procedures. We have therefore focused on reduced port surgery, using only 2-ports. In this study, we compared 2-port laparoendoscopic radical prostatectomy (2-port RP) and conventional 5-port laparoscopic radical prostatectomy (LRP) for clinically localized prostate carcinoma and evaluated the potential advantages of each. From January 2010 to December 2010, all 23 patients with clinically localized prostate cancer underwent LRP. Starting November, 2010, when we introduced the reduced port approach, we performed this procedure for 22 consecutive patients diagnosed with early-stage prostate cancer (cT1c, cT2N0). The patients were matched 1:1 to 2-port RP or LRP for age, preoperative serum PSA level, clinical stage, biopsy and pathological Gleason grade, surgical margin status, pad-free rates and post-operative pain. There was a significant difference in operative time between the 2-port RP and LRP groups (286.5 ± 63.3 and 351.8 ± 72.4 min: p=0.0019, without any variation in blood loss (including urine) (945.1 ± 479.6 vs 1271.1 ± 871.8 ml: p=0.13). The Foley catheter indwelling period was shorter in the 2 port RP group, but without significance (5.6 ± 1.8 vs 8.0 ± 5.6 days: p=0.057) and the total perioperative complication rates for 2 port RP and LRP were comparable at 4.5% and 8.7% (p=0.58). There was an improvement in pad-free rates up to 6 months follow-up (p=0.090), and significantly improvement at 1 year (p=0.040). PSA recurrence was 1 (4.5%) in 2-port RP and 2 (8.7%) in LRP. Continuous epidural anesthesia was used in most of LRP patients (95.7%) and in early 2-port RP patients (40.9%). In these patients, average total amount of Diclofenac sodium was 27.8 mg/patient in 2-port RP and 50.0mg/patient in LRP. Thus the reduced port approach is as efficacious as LRP in terms of many outcome measures, with significant cosmetic advantages and reduction in post surgical pain. This method can be readily performed safely and therefore can be recommended as a standard laparoscopic surgery for prostate cancer in the future.

A Novel PRPF31 Mutation in a Large Chinese Family with Autosomal Dominant Retinitis Pigmentosa and Macular Degeneration

PurposeThis study was intended to identify the disease causing genes in a large Chinese family with autosomal dominant retinitis pigmentosa and macular degeneration.MethodsA genome scan analysis was conducted in this family for disease gene preliminary mapping. Snapshot analysis of selected SNPs for two-point LOD score analysis for candidate gene filter. Candidate gene PRPF31 whole exons' sequencing was executed to identify mutations.ResultsA novel nonsense mutation caused by an insertion was found in PRPF31 gene. All the 19 RP patients in 1085 family are carrying this heterozygous nonsense mutation. The nonsense mutation is in PRPF31 gene exon9 at chr19:54629961-54629961, inserting nucleotide “A” that generates the coding protein frame shift from p.307 and early termination at p.322 in the snoRNA binding domain (NOP domain).ConclusionThis report is the first to associate PRPF31 gene's nonsense mutation and adRP and JMD. Our findings revealed that PRPF31 can lead to different clinical phenotypes in the same family, resulting either in adRP or syndrome of adRP and JMD. We believe our identification of the novel “A” insertion mutation in exon9 at chr19:54629961-54629961 in PRPF31 can provide further genetic evidence for clinical test for adRP and JMD.

Choroidal thickness in retinitis pigmentosa using EDI OCT

AbstractPurpose To describe the choroidal thickness of patients with RP using enhanced depth imaging (EDI) and spectral domain (SD) optical coherence tomography (OCT), comparing with impaired non affected subjects.Methods Prospective, case‐control study of 20 patients with RP imaged using the Spectralis EDI protocol. 40 healthy age‐matched subjects participated in the study as control. RP patients had mild to severe disease, with a visual acuity range of ETDRS 20/20 to light perception. Choroidal thickness measures were determined via manual segmentation of the OCT image. Submacular choroidal thickness measurements were obtained beneath the fovea and at 500 µm intervals for 2.0 mm nasal and temporal to the centre of the fovea. These measurements on RP patients were compared to choroidal thickness measurements from 40 controls with similar refraction and no clinical evidence of retinal or glaucomatous disease. Statistical analysis was performed to compare choroidal thickness at each location between the two groups and to correlate choroidal thickness with best‐corrected visual acuity.Results Mean ages were 47.025 years for control patients and 49.3 years for RP patients (p&gt;0.05). Mean choroidal thickness measurements were 211.9 ± 80 µm in RP patients and 305.6 ± 89 µm in controls (p&lt;0.0001). The thickness gradually decreased toward the peripheral retina in the RP and control patients. It was greater in the temporal field than the nasal one in both groups. All values were highly significantly lower in RP group than those of the controls (p≤0.001). Patients with poorer visual acuity or older (longer duration of disease) tended to have thinner choroidsConclusion Submacular choroidal thickness, as measured by SD–OCT EDI, is significantly reduced in patients comparing with age matched cIontrol

Photoreceptor integrity and visual acuity in retinitis pigmentosa

AbstractPurpose To assess the correlation between the status of the inner segment/outer segment junction (IS/OS) and visual acuity in retinitis pigmentosa.Methods One hundred and ninety‐six eyes of 100 patients with RP were examined with the spectral optical coherence tomography (3D‐OCT‐2000). The status of the inner segment/outer segment junction (IS/OS) (Grade 1: absent, Grade 2: blurred discontinuous, or Grade 3: distinct) was evaluated. Correlation between visual acuity and each of the measurements were examined.Results Of the 196 eyes, IS/OS was absent in 61 eyes (30.9%), blurred in 71 eyes (36.36%) and distinct in 64 eyes (32.74%).Total retinal thickness was not correlated with visual acuity. The mean logMAR visual acuity (VA) in the IS/OS absent group (0.65±0.12) was worse than the one seen in the IS/OS blurred (0.23±0.41) or IS/OS distinct groups (0.08±0.44) (P&lt;0.001). But eighteen per cent of the eyes with a normal foveal IS/OS line, normal COST line and normal perifoveal layers have a bad visual acuity. While seven per cent of eyes with absent foveal IS/OS line have surprisingly a good visual acuity.Conclusion The status of photoreceptor IS/OS line is an important parameter that needs to be examined in RP patients, while perifoveal retinal layers need not be examined. The presence of the foveal photoreceptor IS/OS line is associated with better visual acuity and thicker fovea in RP patients. But, in a few cases, the foveal photoreceptor IS/OS line can be absent with a good visual acuity.

Contribution of SNRNP200 sequence variations to retinitis pigmentosa

Mutations in the SNRNP200 gene have been reported to cause autosomal dominant retinitis pigmentosa (adRP). In this study, we evaluate the mutation profile of SNRNP200 in a cohort of southern Chinese RP patients. Twenty adRP patients from 11 families and 165 index patients with non-syndromic RP with mixed inheritance patterns were screened for mutations in the mutation hotspots of SNRNP200. These included exons 12-16, 22-32, and 38-45, which covered the two helicase ATP-binding domains in DEAD-box and two sec-63 domains. The targeted regions were amplified by polymerase chain reaction and analyzed by direct DNA sequencing, followed by in silico analyses. Totally 26 variants were identified, 18 of which were novel. Three non-synonymous variants (p.C502R, p.R1779H and p.I698V) were found exclusively in patients. Two of them, p.C502R and p.R1779H, were each identified in one simplex RP patient, whereas p.I698V occurred in one patient with unknown inheritance pattern. All three residues are highly conserved in SNRNP200 orthologs. Nevertheless, only p.C502R and p.R1779H were predicted to affect protein function by in silico analyses, suggesting these two variants are likely to be disease-causing mutations. Notably, all mutations previously identified in other study populations were not detected in this study. Our results reveal a distinct mutation profile of the SNRNP200 gene in a southern Chinese cohort of RP patients. The identification of two novel candidate mutations in two respective patients affirmed that SNRNP200 contributes to a proportion of overall RP.

FRI0374 Transition from primary to secondary raynaud’s phenomenon: a capillaroscopy-based prospective study

BackgroundRaynaud’s phenomenon (RP) is classified as primary (PRP) or secondary (SRP) depending on its association with an underlying disease. PRP can evolve to SRP when associated to connective tissue diseases,...

FRI0474 Association of serum vascular endothelial growth factor and angiopoietin-2 levels with clinical manifestations and nailfold capillaroscopic changes in patients with raynaud’s phenomenon

BackgroundRaynaud’s phenomenon (RP) is an exaggerated vasospastic response to cold and emotion, which can be primary (idiopathic) or secondary to a number of different conditions, including rheumatological diseases. Functional and/or...

THU0470 Association of Relapsing Polychondritis with Other Autoimmune Conditions: Experience of a Romanian Center

BackgroundRelapsing polychondritis(RP) is a rare inflammatory disease affecting cartilaginous structures. About one third of the patients with RP have a concurrent or preceding autoimmune disease thus making diagnosis difficult.ObjectivesTo assess...

Correlation of Urinary Engrailed-2 Levels to Tumour Volume and Pathological Stage in Men Undergoing Radical Prostatectomy

The aim of this study was to assess the relationship between pre-prostatectomy urinary Engrailed-2 (EN2), a transcription factor secreted by prostate cancer cells, with tumour volume and pathological characteristics in resected prostate specimens. First pass urine samples (10 ml) without prior prostatic massage were collected and stored at –80°C. EN2 levels were measured using an enzyme-linked immunoabsorbent assay. Tumour volume in the prostatectomy specimens was determined histologically. 57 men undergoing RP in one urological cancer network were evaluated. EN2 was detected in 85% of RP patients. EN2 correlated with tumour volume (but not total prostatic volume) in a linear regression analysis, with increasing pathological T stage and margin positivity. Using three “cutoff levels” of tumour volume (0.5 ml, 1.3 ml and 2.5 ml) to define “significant disease”, men with “significant disease” had markedly higher levels of urinary EN2 (p Levels of urinary EN2 may be useful in predicting tumour volume in men with prostate cancer by potentially identifying men with small volume “insignificant” disease. This study justifies a larger multicentre evaluation of urinary EN2 levels as a biomarker of PC significance using cancer volume, pathological and PSA criteria.

Mutations inRPGRandRP2Account for 15% of Males with Simplex Retinal Degenerative Disease

To determine the proportion of male patients presenting simplex retinal degenerative disease (RD: retinitis pigmentosa [RP] or cone/cone-rod dystrophy [COD/CORD]) with mutations in the X-linked retinal degeneration genes RPGR and RP2. Simplex males were defined as patients with no known affected family members. Patients were excluded if they had a family history of parental consanguinity. Blood samples from a total of 214 simplex males with a diagnosis of retinal degeneration were collected for genetic analysis. The patients were screened for mutations in RPGR and RP2 by direct sequencing of PCR-amplified genomic DNA. We identified pathogenic mutations in 32 of the 214 patients screened (15%). Of the 29 patients with a diagnosis of COD/CORD, four mutations were identified in the ORF15 mutational hotspot of the RPGR gene. Of the 185 RP patients, three patients had mutations in RP2 and 25 had RPGR mutations (including 12 in the ORF15 region). This study represents mutation screening of RPGR and RP2 in the largest cohort, to date, of simplex males affected with RP or COD/CORD. Our results demonstrate a substantial contribution of RPGR mutations to retinal degenerations, and in particular, to simplex RP. Based on our findings, we suggest that RPGR should be considered as a first tier gene for screening isolated males with retinal degeneration.

Exome Sequencing Identifies a Founder Frameshift Mutation in an Alternative Exon of USH1C as the Cause of Autosomal Recessive Retinitis Pigmentosa with Late-Onset Hearing Loss

We used a combined approach of homozygosity mapping and whole exome sequencing (WES) to search for the genetic cause of autosomal recessive retinitis pigmentosa (arRP) in families of Yemenite Jewish origin. Homozygosity mapping of two arRP Yemenite Jewish families revealed a few homozygous regions. A subsequent WES analysis of the two index cases revealed a shared homozygous novel nucleotide deletion (c.1220delG) leading to a frameshift (p.Gly407Glufs*56) in an alternative exon (#15) of USH1C. Screening of additional Yemenite Jewish patients revealed a total of 16 homozygous RP patients (with a carrier frequency of 0.008 in controls). Funduscopic and electroretinography findings were within the spectrum of typical RP. While other USH1C mutations usually cause Usher type I (including RP, vestibular dysfunction and congenital deafness), audiometric screening of 10 patients who are homozygous for c.1220delG revealed that patients under 40 years of age had normal hearing while older patients showed mild to severe high tone sensorineural hearing loss. This is the first report of a mutation in a known USH1 gene that causes late onset rather than congenital sensorineural hearing loss. The c.1220delG mutation of USH1C accounts for 23% of RP among Yemenite Jewish patients in our cohort.

Altered innate functions of myeloid dendritic cells in ANCA-associated vasculitis

Background Dendritic cells (DC) are critical effectors of innate and adaptive immunity, acting both as sentinels that detect the presence of pathogens and as key antigen-presenting cells that regulate the adaptive immune response. Therefore, DC play a crucial role in the control of autoimmune responses. We previously showed that blood DC numbers were strongly reduced in ANCA-associated vasculitis (AAV) likely due to their recruitment in tissues. Here, we assessed the ex vivo responsiveness of blood DC from AAV-patients to Toll-like receptors (TLRs) stimulation. Materials and methods Blood samples from 10 untreated patients with AAV during flares and before any immunosuppressive treatment (AP) were analyzed, along with 9 AAV patients in remission (RP) and 11 age-matched healthy controls (HC). Intracellular cytokine (IL-12, TNF-a ,I FN-a) production by blood DC was assessed by 8-colors flow cytometry after stimulation by Toll-like receptors of whole blood samples. Results We found that myeloid DC (mDC) from patients in acute phase exhibited a decreased IL-12 production after TLR3, 4 and 7/8 stimulation compared to patients in remission and healthy controls. These mDC also produced less TNF-a after TLR3 stimulation. Moreover, we observed a reduction in the frequency TNFa-producing plasmacytoid DC (pDC) upon TLR7/8 triggering in AP patients compared to RP patients and HC. Conclusion

Late appearance and exacerbation of primary Raynaud’s phenomenon attacks can predict future development of connective tissue disease: a retrospective chart review of 3,035 patients

To assess the prognostic value of the age at onset of Raynaud's (RP) and of a history of exacerbation of RP attacks for the development of connective tissue disease (CTD) in patients initially found to have primary Raynaud's. 3,035 patients with primary RP (2,702 women and 333 men) were followed for an average of 4.8 years (range from 1 to 10 years). At baseline and every 6 months, they were screened for signs and symptoms of CTD. At 4.8 years of follow-up, 54.7 % patients remained as primary RP, 8.1 % had developed suspected secondary RP, and 37.2 % had developed a definite CTD. Primary RP patients had an earlier onset of RP (mean age of 32.2 years) than those with suspected (mean age 36.5 years, P = .007) or definite secondary RP associated with CTD (mean age of 39.8 years, P = .004). RP beginning before the age of forty was not significantly associated with the development of CTD. Conversely, the appearance of RP after the age of 40 was significantly associated with the development of CTD (P = .00001). Worsening of RP attacks predicted the development of CTD, especially systemic sclerosis (relative risk [RR] of 1.42), scleroderma overlap syndrome (RR of 1.18), and mixed CTD (RR of 1.18). Patients whose onset of RP occurred past 40 years of age and those with worsening RP attacks were at risk for the future development of CTD.

Transcorneal Electrical Stimulation Promotes Survival of Photoreceptors and Improves Retinal Function in Rhodopsin P347L Transgenic Rabbits

To determine whether transcorneal electrical stimulation (TES) has neuroprotective effects on the photoreceptors, and whether it slows the rate of decrease of the electroretinogram (ERG) in rhodopsin P347L transgenic (Tg) rabbits. Six-week-old Tg rabbits received TES through a contact lens electrode on the left eye weekly for 6 weeks. The right eyes received sham stimulation on the same days. Electroretinograms (ERGs) were recorded before and at 12 weeks after the TES. After the last ERG recordings, the animals were euthanized for morphologic analysis of the retinas. Immunohistochemical (IHC) analysis was performed to detect the immunostaining by peanut agglutinin (PNA) and rhodopsin antibodies in the retinas. The a- and b-wave amplitudes of the photopic ERGs and the b-wave amplitudes of the scotopic ERGs at higher stimulus intensities were significantly larger in the TES eyes than in the sham stimulated eyes (P<0.05, respectively). Morphologic analyses showed that the mean thickness of the outer nuclear layer (ONL) in the visual streak at 12 weeks was significantly thicker in TES eyes than in sham-stimulated eyes (P<0.05). IHC showed that the immunostaining by PNA and rhodopsin antibody in the TES-treated retinas was stronger than that in the sham-stimulated retinas. TES promotes the survival of photoreceptors and preserves the ERGs in Tg rabbits. Although further investigations are necessary before using TES on patients, these findings indicate that TES should be considered for therapeutic treatment for RP patients with a P347L mutation of rhodopsin.