[Characteristics of gastric mucosa microbiota in children with chronic gastritis and duodenal ulcer].

Objective: To investigate the differences of gastric mucosa microbiota between children with chronic gastritis and duodenal ulcer under the condition of Helicobacter pylori (Hp) infection. Methods: This prospective cohort study involved 57 children with Hp infection diagnosed by gastric endoscopy who were admitted to the Children's Hospital of Zhejiang University School of Medicine due to "abdominal pain, abdominal distension and vomiting" between January 2018 to August 2018. According to gastroscopy and pathological examination, the children were divided into chronic gastritis group and duodenal ulcer group. Gastric mucosa from Hp infected patients were sampled, and the flora DNA was analyzed by high-throughput sequencing. The statistical difference of α diversity, ß diversity between two groups were analyzed. The relative abundance of the two groups in each taxonomic level was analyzed statistically. T test, Rank sum test or χ2 test was used for comparison between the two groups. Results: A total of 57 children diagnosed with Hp infection were enrolled in this study, including 42 cases of chronic gastritis (the age was (9.3±2.8) years, 22 males and 20 females) and 15 cases of duodenal ulcer (the age was (11.1±3.3) years, 9 males and 6 females). Alpha diversity index Chao and ACE in Hp infected chronic gastritis group were significantly higher than those in Hp infected duodenal ulcer group (217±50 vs. 183±64, t=2.088, P=0.009;218±47 vs. 192±76, t=1.566, P=0.016, respectively). The Beta-diversity index such as nonmetric multidimensional scaling (NMDS) analysis were significantly different in the two groups (analysis of similarity R=0.304, P=0.028). Among the main bacteria genera, there were 6 genera with significant differences between the two groups, which were Prevotella (0.190% (0.008%-1.983%) vs. 0.021% (0.005%-2.398%), Z=-2.537, P=0.011), Alloprevotella (0.097% (0.010%-0.813%) vs. 0.015% (0.003%-0.576%), Z=-2.492, P=0.013), Haemophilus (0.109% (0.004%-0.985%) vs. 0.014% (0.004%-0.356%), Z=-2.900, P=0.004), Neisseria (0.074% (0.004%-0.999%) vs. 0.024% (0.003%-0.255%), Z=-2.718, P=0.007), Streptococcus (0.166% (0.008%-1.869%) vs. 0.045% (0.006%-0.879%), Z=-2.537, P=0.010), and an unclassified-Microbacteriaceae (0.214% (0.060%-1.762%) vs. 0.117% (0.010%-0.954%), Z=-2.120, P=0.034). Linear discriminant analysis (LDA) effect sized analysis showed that at the genus level, only Prevotella was significantly enriched in the duodenal ulcer group (LDA=2.90, P=0.010), while Streptococcus, Neisseria and Haemophilus were significantly enriched in the chronic gastritis group (LDA=2.83, 2.82, 2.69, P=0.011, 0.007, 0.004, respectively). Conclusions: The gastric mucosal microbiota in duodenal ulcer associated with Hp is significantly different from that in chronic gastritis. Hp may promote the occurrence of peptic ulcer together with gastric microbiota.

[Situation of coal dust hazards and its damage of pulmonary function of a large-scale coal mine enterprise of Shanxi province].

Objective: To investigate the status of coal dust hazard classification and lung function damage in a large coal mine in Shanxi Province. Methods: From January to June in 2019, 51 coal dust posts and 598 workers exposed to coal dust were selected from a large coal mine enterprise in Shanxi Province. The coal dust (exhaled dust) samples were collected and tested, and the hazard classification index of coal dust (exhaled dust) was calculated. The jobs exposed to coal dust (exhaled dust) were divided into relatively harmless, mild, moderate and severe hazard posts, and the corresponding workers were divided into relatively harmless group, mild, moderate and severe hazard groups. The forced expiratory volume (FEV1) , forced vital capacity (FVC) and forced expiratory volume/forced vital capacity (FEV1/FVC) in the first second were measured. Spearman rank correlation method was used to analyze the relationship between the hazard grade of coal dust and lung function. Results: Among 51 coal dust (exhalation) posts, 13 coal dust (exhalation dust) exceeded the standard (25.5%) . 168 cases (34.78%) had abnormal pulmonary function. Compared with the relatively harmless group, the proportion of abnormal pulmonary function of workers in mild, moderate and severe hazard groups were higher, FEV1, FVC, FEV1/FVC values were lower, the differences were statistically significant (P<0.05) . The rank of coal dust (exhaled dust) was negatively correlated with FEV1, FVC and FEV1/FVC (P<0.01) . Conclusion: Attention should be paid to the supervision and management of relatively harmless and slightly harmful coal dust posts. FVC may be one of the lung function indexes sensitive to coal dust exposure.

[Effect of enteral nutrition on accidental upper gastrointestinal injury in children].

Objective: To evaluate the effectiveness of enteral nutrition in children with accidental upper gastrointestinal injury. Methods: The medical records of 128 patients with mechanical or chemical gastrointestinal mucosal injury, who were hospitalized in Department of Gastroenterology, Children's Hospital of Zhejiang University School of Medicine from January 1, 2011 to December 30, 2017, were collected. All cases were treated with enteral nutrition. The clinical features and etiologies were retrospectively analyzed. Weight-for-age Z score and lab findings including white blood cells, C-reactive protein, neutrophils, albumin, prealbumin, urea nitrogen and hemoglobin before and after treatment were extracted. The clinical characteristics, the duration of enteral nutrition and gastrointestinal mucosal healing between different etiologies were further analyzed. Normal distribution variables and categorized variables were compared with t test and χ(2) test respectively, and abnormal distribution data was compared with Wilcoxon test. Results: Among all the cases, 77 were males and 51 were females. The average age was (29±22) months. The mean duration of hospitalization and enteral nutrition were (11±7)d and (27±20)d respectively. Vomiting was the most common clinical presentation (72 cases, 56.3%). In 79 cases the problems were caused by mechanical injury, among which coins were most commonly seen. The rest 49 cases were caused by chemical injury. However, the duration of hospitalization ((13±8) d vs. (10±6)d, t=-3.089, P=0.002) and enteral nutrition ((39±22) vs. (19±14) d, t=-5.365, P=0.000) were longer in children with chemical injury than those with mechanical injury. A total of 112 cases got complete blood count and C-reactive protein both before and after enteral nutrition. Inflammatory markers, including leukocytes ((7.7±2.7) ×10(9)/L vs. (13.7±5.0) ×10(9)/L, t=12.244, P <0.05), neutrophils ((3.4±1.9)×10(9)/L vs. (9.4±4.6) ×10(9)/L, t=13.655, P<0.05), and C-reactive proteins (5.0(3.0,7.8) vs. 13.5(6.0,40.5) mg/L, Z=7.776, P <0.05) were significantly decreased. The nutritional markers, including the weight-for-age z score (-0.1 ± 1.0 vs. 0.0 ± 1.0, t=-2.622, P=0.010) and the prealbumin (0.1 ± 0.1 vs. 0.2 ± 0.0 g/L, t=-3.671, P=0.001) were significantly increased. Fifty-five (82.1%) children in mechanical injury group recovered in 4 weeks, while 27 (79.4%) children in chemical injury group recovered in 7 weeks. Conclusion: Enteral nutrition can provide adequate nutritional requirements for children with upper gastrointestinal injury, and may help to decrease imflammation and improve mucosal healing.

Removing a metal foreign object successfully from a patient's retroperitoneal space using laparoscopy and a novel navigation system.

Trauma with foreign objects retained within the human body has become a common surgical emergency condition. Traditional surgical methods often involve creating large incisions in soft tissue and may lead to additional complications during wound healing. We have developed a new method of removing foreign bodies from patients' abdomens by using laparoscopy with the help of a novel navigation system that provides accurate positioning. This approach is minimally invasive and simple. This is the first combination of both technologies in this field.

[Eosinophilic esophagitis in children: analysis of 22 cases].

Objective: Eosinophilic esophagitis (EoE) is a chronic immune-mediated esophageal disease.The current domestic reports of EoE in children is rare.The aim of this study was to analyze the clinical features, the diagnosis and treatment advance of EoE in children by case analysis and literature review. Method: Clinical data of 22 children with EoE from January, 2011 to December, 2015 in Children's Hospital, Zhejiang University School of Medicine were recorded, retrospective analysis was performed on clinical presentation, gastroendoscopy and histopathological examination features and the treatment. Result: (1) Clinical data: EoE can occur at any age in children (5 months to 13 years). The most common clinical manifestations of EoE are vomiting and abdominal pain, 45% (10/22) and 41%(9/22) respectively. (2) Endoscopy and pathological features of esophageal mucosa: 11 cases with coarse mucous membrane (50%), 6 cases with congestion or erosion of esophageal membrane (27%), 5 cases with longitudinal crack (23%), 3 cases with ring uplift (14%), 3 cases with granular uplift (14%), 3 cases with normal mucosa(14%). Histopathologic manifestation is eosinophil infiltration and the eosinophil counts were all more than or equal to 15/HP. (3) Laboratory results: 13 cases had increasing eosinophil counts and eosinophils proportion (62%). (4)Allergy history: among 22 cases, 7 patients had allergy history (32%). (5) Situation of treatment and remission: 16 cases had clinical remission by oral omeprazole; 2 cases had clinical remission by oral Omeprazole and Montelukast sodium; 1 case acquired remission by elimination diet; 1 case acquired remission by elimination diet and oral prednisone. 2 cases dropped out; Only 2 patients received gastroendoscopy re-examination after 3 months and revealed esophageal mucosal histologic complete recovery. Conclusion: The clinical symptoms of EoE in children varies.Esophageal mucosal features of gastroendoscopy examination in children with EoE were longitudinal crack, white exudates or plaques, paper mucosa, ring uplift and granular uplift.Most patients could achieve remission by using proton-pump inhibitors, only few children needed elimination diet and change formula, or even oral glucocorticoids.

Efficacy of minimally invasive tonsil surgery for treatment of obstructive sleep apnea-hypopnea syndrome in children.

This study aimed to investigate the efficacy of minimally invasive tonsil surgery for the treatment of obstructive sleep apnea-hypopnea syndrome (OSAHS) in children. Tonsil ablation or turbinate reduction was performed on 49 pediatric patients with OSAHS by minimally invasive tonsil surgery. In order to evaluate the efficacy of surgery, a comparison was conducted between pre-operation and post-operation data in terms of the symptoms, signs and polysomnography test. Total effectiveness rate of the surgery was 83.7%. Subgroup analysis was also performed based on the severity of their conditions: mild, moderate, and severe groups had an effectiveness rate of 90.0, 88.9, and 66.7%, respectively (Hc=6.665, P<0.05). Postoperatively, the apnea-hypopnea index, the minimum oxygen saturation (SaO2), and corresponding symptoms improved compared to pre-operation conditions (P<0.05). Minimally invasive tonsil surgery was a safe and effective method for treating OSAHS in children.

[A bibliometric analysis of literature on hand-transmitted vibration in China, 1990-2016].

Objective: To investigate the features of literature on hand-transmitted vibration in China, 1990-2016. Methods: In September 2017, the studies on hand-transmitted vibration in China, which were published in Chinese or English during 1990-2016, with "China" and "Taiwan" as the places where author affiliations were located, were retrieved. A bibliometric analysis was performed to investigate the type of articles, publication time, the journals in which articles were published, author affiliations, author regions, and funding. Results: A total of 205 articles on hand-transmitted vibration were retrieved. There were 7.59 articles on average published annually from 1990 to 2016. In the 205 articles, 114 (55.61%) were published in the journals indexed in one or two core journal databases. In the 64 journals, 22 (34.38%) were indexed in one or two core journal databases. The first authors were from 22 provincial regions (provinces, autonomous regions, or centrally administered municipalities) in China, with 152 articles (74.15%) by the authors in the top five regions. There were a total of 876 authors, and the co-authorship degree was 4.27 (876/205). Most of the first authors (136 articles, 66.34%) were affiliated with universities or institutes for prevention and control of occupational diseases. Among the 205 articles, 103 (50.24%) were original articles or investigations, and 72 (35.12%) were funded. Conclusion: The studies on hand-transmitted vibration fluctuated and increased from 1990 to 2016, with a relatively concentrated distribution in terms of sources, regions, and institutions. Interregional and international academic exchange should be strengthened.

A novel mutation of PAX6 identified in a Chinese twin family with congenital aniridia complicated with nystagmus.

Genetic variations within the paired box gene 6 (PAX6) gene are associated with congenital aniridia. To detect the genetic defects in a Chinese twin family with congenital aniridia and nystagmus, exons of PAX6 were amplified by polymerase chain reaction (PCR), sequenced and compared with a reference database. Six members from the family of three generations were included in the study. The twins' father presented with congenital aniridia, nystagmus and cataract at birth, while the twins presented with congenital aniridia and nystagmus. A novel mutation c.888 insA in exon 10 of PAX6 was identified in all affected individuals. This study suggests that the novel mutation c.888 insA is likely responsible for the pathogenesis of the congenital aniridia and nystagmus in this pedigree. To the best of our knowledge, this is the first report of this mutation in PAX6 gene in pedigree with aniridia. Furthermore, no PAX6 gene defect was reported in twins with congenital aniridia.

Initial and middle-term results of treatment for symptomatic spontaneous isolated dissection of superior mesenteric artery.

OBJECTIVE: Spontaneous isolated dissection of the superior mesenteric artery (SIDSMA) is extremely rare. Various treatment options are currently available, including conservative treatment, endovascular stenting (ES) and surgical repair. Herein, we present our experience in the treatment of symptomatic SIDSMA. METHODS: A retrospective study was conducted on 17 consecutive patients with symptomatic SIDSMA from May 2002 to May 2012. Conservative treatment consisted of strict blood-pressure control, bowel rest, nasogastric suction, intravenous fluid therapy and nutritional support as required; fasting was released on resolution of abdominal pain, and fluid food was given first; then, diet was resumed after complete resolution of abdominal pain. The decision to intervene was based on patient symptoms and signs, as well as the morphological characteristics of SMA dissection on computed tomography (CT) angiography. Self-expandable stents were placed via the common femoral artery approach. ES was indicated in patients with severe compression of the true lumen or dissecting aneurysm likely to rupture. RESULTS: All patients had acute-onset abdominal pain. Treatment included conservative treatment with the use of anticoagulation in five and without in nine patients, respectively. Three patients with severe compression of the true lumen or large dissecting aneurysm underwent ES as a primary treatment. ES was performed in two patients in whom initial conservative treatment failed. Patients who underwent ES were maintained on anti-platelet therapy for 3 months postoperatively. The median follow-up time was 24 months (range, 2-72 months). No complications were associated with the SIDSMA or ES. The patency of stents was demonstrated on follow-up CT scans up to 8.5 months (range, 4-38 months). CONCLUSIONS: Conservative treatment without anticoagulation can be applied successfully to the patients with symptomatic SIDSMA. Our strategy of restricting ES for these patients who have compression of the true lumen or dissecting aneurysm likely to rupture (and for those with failed conservative treatment) was successful.

Overexpression of Csk-binding protein contributes to renal cell carcinogenesis.

C-terminal Src kinase (Csk)-binding protein (Cbp) is a transmembrane adaptor protein that localizes exclusively in lipid rafts, where it regulates Src family kinase (SFK) activities through recruitment of Csk. Although SFKs are well known for their involvement in cancer, the function of Cbp in carcinogenesis remains largely unknown. In this study, we reported overexpression of Cbp in more than 70% of renal cell carcinoma (RCC) specimens and in the majority of tested RCC cell lines. Depletion of Cbp in RCC cells by RNA interference led to remarkable inhibition of cell proliferation, migration, anchorage-independent growth as well as tumorigenicity in nude mice. Strikingly, silencing of Cbp negatively affected the sustaining of Erk1/2 activation but not c-Src activation induced by serum. Besides, the RhoA activity in RCC cells was remarkably impaired when Cbp was knocked down. Overexpression of wild-type Cbp, but not its mutant Cbp/DeltaCP lacking C-terminal PDZ-binding motif, significantly enhanced RhoA activation and cell migration of RCC cells. These results provided new insights into the function of Cbp in modulating RhoA activation, by which Cbp might contribute to renal cell carcinogenesis.

The association of CTLA-4 and CD28 gene polymorphisms with idiopathic ischemic stroke in the paediatric population.

Autoimmune vasculitis is believed to be a critical factor in the development of idiopathic childhood ischemic stroke. The association of polymorphisms in CTLA-4 and CD28 with some immune vasculitides, such as systemic lupus erythematosus (SLE) and Behçet's disease has been reported. The aim of the present study is to investigate the association of the genetic variants in the CTLA-4 and CD28 genes of children who suffered idiopathic ischemic stroke using a case-control design. Two single nucleotide polymorphisms (SNPs) in the CTLA-4 gene and an SNP in the CD28 gene were genotyped in 51 patients who suffered idiopathic ischemic stroke, and in 74 healthy controls from mainland China. An SNP, CTLA-4+49A/G located in exon 1 of the CTLA-4 gene, showed nominal association with the disease (P = 0.012, odds ratio (OR) = 2.09, 95% confidence interval (CI) = 1.17-3.73) using allele-based analysis. Homozygous carriers of the G allele of this SNP were more common in the patients than in the controls (P = 0.008). The CD28IVS3 +17TT genotype was found to be more common in the patients than in the controls (P = 0.039, OR = 2.96, 95% CI = 1.02-8.58). No correlations of at-risk genotype (G/G) of CTLA-4+49A/G and genotype (T/T) of CD28+17T/C with the main clinical features of idiopathic childhood ischemic stroke were observed. The results suggest that polymorphisms in the CTLA-4 and CD28 genes may contribute to the increased risk of idiopathic ischemic stroke.

Csk-binding protein (Cbp) negatively regulates epidermal growth factor-induced cell transformation by controlling Src activation.

Epidermal growth factor receptor (EGFR) and Src tyrosine kinase cooperate in regulating EGFR-mediated cell signaling and promoting cell transformation and tumorigenesis in pathological conditions. Activation of Src is tightly regulated by the C-terminal Src kinase (Csk). The Csk-binding protein (Cbp) is a ubiquitously expressed transmembrane protein. Its functions include suppression of T-cell receptor activation through recruiting Csk and inhibiting Src family kinase (SFK). However, a potential role of Cbp in EGF-induced cell activities has not been investigated. Here, we report that EGF-stimulation-induced Cbp tyrosine phosphorylation followed by Cbp-Csk association, in a SFK-dependent manner. Expression of wild-type (wt) Cbp remarkably suppressed EGF-induced activation of Src, ERK1/2, and Akt-1 enzymes, and NIH3T3 cell transformation, as well as colony formation of a breast cancer cell line (MDA-MB-468) in soft agar. In contrast, expression of CbpY317F or knockdown endogenous Cbp in NIH3T3 cells by RNA interference significantly enhanced EGF-induced activation of these enzymes and cell transformation. In addition, overexpression of multiple receptor tyrosine kinases (RTKs)-induced Cbp tyrosine phosphorylation. These results demonstrate that Cbp functions as a negative regulator of cell transformation and tumor cell growth through downregulation of Src activation, suggesting that Cbp might be broadly involved in RTKs-activated signaling pathways and tumorigenesis.

Effect of cyclosporine on anterior chamber-associated immune deviation with retinal transplantation.

PURPOSE: To determine whether immunosuppression using cyclosporine interferes with anterior chamber associated immune deviation (ACAID) and can promote survival of retinal allografts in the anterior chamber. METHODS: Neonatal neural retinas of C57BL/6 mice or ovalbumin were injected into the anterior chamber of BALB/c adult mice. In the test group recipients were injected with cyclosporine (10 mg/kg per day) from day 0 to 11 or from day 11 to 34 after implantation. At 12 and 35 days after transplantation, lymphocytes from the test group were injected into naive BALB/c mice to assay for the presence of suppressor T cells (adoptive transfer). The fate of the retinal grafts was determined by histologic examination at day 12 and 35. To evaluate the potential neurotoxic effects of cyclosporine in the absence of immune rejection mechanisms, cyclosporine was given to SCID mice during days 11 to 34 after syngeneic neonatal neural retinal grafts were placed in the anterior chamber. RESULTS: At 12 days after transplantation, spleens of both cyclosporine-treated and control mice contained suppressor cells against donor alloantigens. The retinal grafts in the anterior chamber of both groups of mice were fully developed and well differentiated. The same duration of administration of cyclosporine did not interfere with the production of efferent suppressor cells after inoculation of ovalbumin into the anterior chamber. At 35 days after transplantation, only spleen cells from the cyclosporine-treated group showed the capacity to suppress donor-specific delayed hypersensitivity. However, allografts in the cyclosporine group had deteriorated by 35 days in a fashion similar to the control group. Syngeneic grafts in SCID mice showed differentiated retinal layers 35 days after transplantation. CONCLUSIONS: Cyclosporine treatment does not interfere with the ability of allogeneic neonatal retinal grafts to induce anterior chamber associated immune deviation when placed in the anterior chamber, nor does prolonged treatment with this drug interfere with the persistence of allospecific suppressor cells for 35 days after the graft. Because 35-day grafts of cyclosporine-treated mice display histologic evidence of graft failure similar to grafts placed in the anterior chamber of untreated mice, graft destruction is either the result of immune effector mechanisms not inhibited by cyclosporine, or the consequence of nonimmunologic factors.

Immunity and immune privilege elicited by cultured retinal pigment epithelial cell transplants.

PURPOSE: To determine whether cultured retinal pigment epithelial (RPE) cells implanted in the subconjunctival space induce an immune response against autoantigens and whether an active downregulation is achieved by RPE grafts placed in the anterior chamber and within the subretinal space. METHODS: Cultured RPE cells from eyes of newborn C57BL/6 mice were implanted in the subconjunctival space, the anterior chamber, or the subretinal space of eyes of adult C57BL/6 mice. At postimplantation day 12, the recipients were evaluated for RPE-specific delayed hypersensitivity and examined clinically and histologically for evidence of rejection. To facilitate their identification, RPE cells were labeled with 5-bromodeoxyuridine, before intraocular transplantation. RESULTS: Cultured RPE cells implanted in the subconjunctival space of syngeneic mice elicited an intense RPE-specific delayed hypersensitivity associated with a vehement cellular infiltration of the graft when examined at postimplantation day 12. By contrast, grafts in the anterior chamber and subretinal space displayed no evidence of rejection, and their recipients failed to display RPE-specific delayed hypersensitivity. Additionally, the spleens of these mice contained regulatory T cells that suppressed RPE-specific delayed hypersensitivity in naive syngeneic recipients. CONCLUSIONS: Cultured RPE cells can induce an immune response against autoantigens. Implantation of RPE cells in immune-privileged sites of the eye induces a deviant immune response that is associated with spleen cells that suppress RPE-specific delayed hypersensitivity and autoimmune rejection.

Unconventional rejection of neural retinal allografts implanted into the immunologically privileged site of the eye.

The unique feature of neural transplantation in the central nervous system is that the graft is derived from and implanted into an immunologically privileged site. The eye, as a part of the central nervous system, normally maintains an immunosuppressive microenvironment in which alloantigens induce an active down-regulation of specific delayed hypersensitivity. To determine whether neural retinal allografts are eventually rejected and, if so, what type of immunity is associated with rejection, we implanted allogeneic and syngeneic newborn neural retinal grafts into the anterior chamber of the eyes of immune-competent mice. In addition, similar allografts were implanted into severe combined immune-deficient (SCID) mice. The fate of these grafts was determined by clinical and histological examination. At post-implantation day 12, all allogeneic and syngeneic grafts survived comparably well with no evidence of inflammation. At post-implantation day 35, the syngeneic grafts in the immune-competent mice and the allogeneic grafts in the SCID mice continued to thrive, whereas the allografts in the immune-competent mice were remarkably reduced in size and had lost the organization of their retinal cell layers. Interestingly, these grafts' deterioration occurred with no obvious cellular infiltration. When systemic graft-specific immunity was examined, it was found that delayed hypersensitivity was impaired at post-implantation day 12 in allograft recipients. However, by post-implantation 35 day when deterioration was detected in these grafts, suppression of immunity was replaced by vigorous delayed hypersensitivity. These results suggest that intraocular retinal allografts eventually succumb to rejection and that rejection is correlated with the emergence of donor-specific delayed hypersensitivity. The possible relationships of atypical, chronic rejection of intraocular neural retinal allografts to emergent delayed hypersensitivity are discussed.

Corneal electroretinographic function rescued by normal retinal pigment epithelial grafts in retinal degenerative Royal College of Surgeons rats.

PURPOSE: This study was designed to examine whether retinal function can be rescued by allogeneic normal retinal pigment epithelial (RPE) grafts in Royal College of Surgeons (RCS) with retinal degeneration and, if so, whether this rescued function can be measured and followed by recording the corneal electroretinogram (ERG). METHODS: RPE donors were RCS-Long Evans crossbred F1 rats with phenotypically normal retinas. Half an RPE sheet was implanted in the subretinal space of RCS rats at postnatal day 20. The fundi of the recipients' eyes were examined, and the corneal ERGs were recorded. The eyes were also examined histologically. RESULTS: The RPE grafts were identified by fundus examination in all 21 recipients. No clinical or histologic evidence of inflammation was detected in the media or the retina of the host eye. Eighteen of 21 (86%) recipients showed rescued corneal ERG function. In nine recipients, the PIII response in the grafted eye was significantly greater than in the nongrafted eye. In the other nine recipients, the ERG in the grafted eye showed a b-wave and an a-wave, whereas no b-wave was detected in the nongrafted eye. Recipients of the sham operation (n = 13) revealed no ERG function rescue. To determine long-term corneal ERG function in RPE recipients, 8 of 18 animals in which ERG function was rescued were randomly selected for continued observation. These recipients sustained rescued ERG function for 16 to 17 weeks, at which time the experiment ended. CONCLUSION: Results indicate that retinal function of degenerative RCS rats, as measured by corneal ERG, can be rescued by implantation of allogeneic normal RPE into the subretinal space of the eye. Furthermore, this rescued function can be followed up over a relatively long period of time, thus providing a useful model for studying the functional changes of RPE allografts resulting from either immunologic or neurobiologic influences.

Immune privilege in the eye: an evolutionary adaptation.

The purpose of this study was to determine whether immune privilege exists in the eye of goldfish and to explore from an evolutionary point of view the relationship between the immunological and neurobiological microenvironments in the eye. Neural retinal or scale allografts and autografts were implanted into the vitreous cavity or the anterior chamber of goldfish eyes. Histological examinations were conducted to determine the fate of these grafts. In order to detect donor-specific immune suppression induced by intraocular retinal allografts, scale allografts obtained from the same donors were subsequently implanted orthotopically and evaluated. Neural retinal allografts implanted intraocularly were rapidly rejected by postimplantation day 8. In contrast, neural retinal autografts survived well within the eye with no inflammation. Prior intraocular allografts, either scale or retinal grafts, did not prevent rejection of subsequent scale allografts nor did they induce down-regulation of systemic immunity. Thus, immune privilege does not exist in the goldfish eye, implying that immune privilege in the eye (or central nervous system) may be an evolutionary adaptation acquired by higher vertebrates. Considering that the capacity for neural regeneration in the central nervous system diminishes during evolution, the hypothesis that immune privilege and neural regeneration may be mutually exclusive properties is addressed.